Pag. 5 Hum Reprod. 2010 Sep 30. [Epub ahead of print] Pigmentary traits and risk of endometriosis. Kvaskoff M, Bijon A, Mesrine S, Clavel-Chapelon F, Boutron-Ruault MC. Inserm, Centre for Research in Epidemiology and Population Health (CESP), U1018, 'Nutrition, Hormones, and Women's Health' Team, Institut Gustave Roussy, F-94805 Villejuif, France. Fertil Steril. 2010 Sep 29. [Epub ahead of print] Postoperative medical treatment of chronic pelvic pain related to severe endometriosis: levonorgestrel-releasing intrauterine system versus gonadotropin-releasing hormone analogue. Bayoglu Tekin ...
Orv Hetil. 2016 Dec;157(49):1960-1966.
Bowel endometriosis: new challenge for gastroenterology and surgery? Three cases of endometriosis caused large bowel ileus and review of the literature.
A number of the patients suffer from endometriosis increased in the past decades and the cases have became more serious. The most critical complication of bowel endometriosis is the large bowel obstruction. Up to recently, 16 similar case reports of large bowel endomteriosis causing obstruction, with detailed medical history have been published in the literature in English language.
Since 2007 535 female have been treated in the 1st Gynaecological Department with endometriosis, out of them three patients from emergency surgery in the history because of large bowel obstruction.
Symptoms suggesting endometriosis or previous intervention due to endometriosis were detected in 59% (13/21) of the cases. Preoperative ultrasound, computertomography, magnetic resonance imaging did not give correct diagnosis. Colonoscopy was carried out before the primary operation in 61% (13/21) and after the surgery in 24% (5/21) of the cases, but none of them confirmed endometriosis. Although all the patients developed obstruction, only in 5% (1/19) of the patients was the mucosa infiltrated by the endometriosis.
In a young female patient, intestinal obstruction can be caused by bowel endometriosis. Identification of colonoscopic signs (rigidity, impression, kinking) of endometriosis may help to avoid unnecessary extension of intestinal resection. Gynaecologists should take part in the operations. Orv. Hetil., 2016, 157(49), 1960-1966.
J Cell Biochem. 2017 Jun;118(6):1547-1555.
Resveratrol Inhibits Proliferation, Invasion, and Epithelial-Mesenchymal Transition by Increasing miR-200c Expression in HCT-116 Colorectal Cancer Cells.
colorectal cancer (CRC) is one of the most common malignancies, associated with high rates of relapse. A notable challenge in treatment is low response rate to current therapies for advanced CRC. The miR-200c plays an essential role in tumor suppression by inhibiting epithelial-mesenchymal transition (EMT). Resveratrol, a natural compound found in red wine, reveals anti-cancer properties in several types of cancers such as CRC. The aim of current study was to evaluate the effects of resveratrol on proliferation, apoptosis, and invasion of HCT-116 cells and also expression of EMT-related genes in presences or absence of miR-200c.
the effect of resveratrol on viability was examined by MTT assay. LNA-anti-miR-200c transfection of HCT-116 cells was carried out in a time dependent manner. Then, the expression of miR-200c and EMT-related genes were quantified by qRT-PCR. Further, expression of EMT-related proteins, apoptosis, and invasion were analyzed by Western blot, Annexin V/PI staining and scratch test, respectively.
resveratrol could significantly inhibit viability of HCT-116 cells. LNA-anti-miR-200c suppressed the endogenous miR-200c in transfected cells compared with the control. qRT-PCR and Western blot analysis of LNA-anti-miR-200c transfected cells revealed a considerable increase in vimentin and ZEB-1 expression, with a concomitant reduction in E-cadherin expression level. Migration of HCT-116 cells increased, and apoptosis significantly reduced in transfected cells. While, resveratrol could entirely reverse these changes by modulation of miR-200c expression.
our findings revealed a major role of resveratrol in apoptosis, invasion, and switching of EMT to MET phenotype through upregulation of miR-200c in CRC. J. Cell. Biochem. 118: 1547-1555, 2017. © 2016 Wiley Periodicals, Inc.
Hum Reprod. 2017 Feb;32(2):315-324.
World Endometriosis Society consensus on the classification of endometriosis.
Johnson NP1,2,3,4, Hummelshoj L5,6, Adamson GD6,7, Keckstein J8, Taylor HS9, Abrao MS5,10, Bush D11, Kiesel L5,12, Tamimi R13, Sharpe-Timms KL5,14, Rombauts L5,15, Giudice LC; for the World Endometriosis Society Sao Paulo Consortium.
What is the global consensus on the classification of endometriosis that considers the views of women with endometriosis?
We have produced an international consensus statement on the classification of endometriosis through systematic appraisal of evidence and a consensus process that included representatives of national and international, medical and non-medical societies, patient organizations, and companies with an interest in endometriosis.
WHAT IS KNOWN ALREADY:
Classification systems of endometriosis, developed by several professional organizations, traditionally have been based on lesion appearance, pelvic adhesions, and anatomic location of disease. One system predicts fertility outcome and none predicts pelvic pain, response to medications, disease recurrence, risks for associated disorders, quality of life measures, and other endpoints important to women and health care providers for guiding appropriate therapeutic options and prognosis.
STUDY DESIGN, SIZE, DURATION:
A consensus meeting, in conjunction with pre- and post-meeting processes, was undertaken.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
A consensus meeting was held on 30 April 2014 in conjunction with the World Endometriosis Society’s 12th World Congress on Endometriosis. Rigorous pre- and post-meeting processes, involving 55 representatives of 29 national and international, medical and non-medical organizations from a range of disciplines, led to this consensus statement.
MAIN RESULTS AND THE ROLE OF CHANCE:
A total of 28 consensus statements were made. Of all, 10 statements had unanimous consensus, however none of the statements was made without expression of a caveat about the strength of the statement or the statement itself. Two statements did not achieve majority consensus. The statements covered women’s priorities, aspects of classification, impact of low resources, as well as all the major classification systems for endometriosis. Until better classification systems are developed, we propose a classification toolbox (that includes the revised American Society for Reproductive Medicine and, where appropriate, the Enzian and Endometriosis Fertility Index staging systems), that may be used by all surgeons in each case of surgery undertaken for women with endometriosis. We also propose wider use of the World Endometriosis Research Foundation Endometriosis Phenome and Biobanking Harmonisation Project surgical and clinical data collection tools for research to improve classification of endometriosis in the future, of particular relevance when surgery is not undertaken.
LIMITATIONS, REASONS FOR CAUTION:
This consensus process differed from that of formal guideline development, although based on the same available evidence. A different group of international experts from those participating in this process may have yielded subtly different consensus statements.
WIDER IMPLICATIONS OF THE FINDINGS:
This is the first time that a large, global, consortium-representing 29 major stake-holding organizations, from 19 countries – has convened to systematically evaluate the best available evidence on the classification of endometriosis and reach consensus. In addition to 21 international medical organizations and companies, representatives from eight national endometriosis organizations were involved, including lay support groups, thus generating and including input from women who suffer from endometriosis in an endeavour to keep uppermost the goal of optimizing quality of life for women with endometriosis.
STUDY FUNDING/COMPETING INTERESTS:
The World Endometriosis Society convened and hosted the consensus meeting. Financial support for participants to attend the meeting was provided by the organizations that they represented. There was no other specific funding for this consensus process. Mauricio Abrao is an advisor to Bayer Pharma, and a consultant to AbbVie and AstraZeneca; G David Adamson is the Owner of Advanced Reproductive Care Inc and Ziva and a consultant to Bayer Pharma, Ferring, and AbbVie; Deborah Bush has received travel grants from Fisher & Paykel Healthcare and Bayer Pharmaceuticals; Linda Giudice is a consultant to AbbVie, Juniper Pharmaceutical, and NextGen Jane, holds research grant from the NIH, is site PI on a clinical trial sponsored by Bayer, and is a shareholder in Merck and Pfizer; Lone Hummelshoj is an unpaid consultant to AbbVie; Neil Johnson has received conference expenses from Bayer Pharma, Merck-Serono, and MSD, research funding from AbbVie, and is a consultant to Vifor Pharma and Guerbet; Jörg Keckstein has received a travel grant from AbbVie; Ludwig Kiesel is a consultant to Bayer Pharma, AbbVie, AstraZeneca, Gedeon Richter, and Shionogi, and holds a research grant from Bayer Pharma; Luk Rombauts is an advisor to MSD, Merck Serono, and Ferring, and a shareholder in Monash IVF. The following have declared that they have nothing to disclose: Kathy Sharpe Timms; Rulla Tamimi; Hugh Taylor.
Reprod Sci. 2017 Aug;24(8):1195-1202.
Serum miR-451a Levels Are Significantly Elevated in Women With Endometriosis and Recapitulated in Baboons ( Papio anubis) With Experimentally-Induced Disease.
We have previously demonstrated that human microRNA-451a (miR-451a) endometriotic lesion expression is significantly higher compared to that of the corresponding eutopic endometrium. The objective of the current study was to examine the relationship between lesion and serum content of miR-451a and to determine the utility of serum miR-451a in distinguishing between women with and without visible signs of endometriosis. Eighty-one participants were enrolled in this study, 41 with confirmed endometriosis and 40 without visible signs of endometriosis at laparoscopy (n = 20) or symptoms of endometriosis (pain, infertility n = 20). Experimental endometriosis was also induced in 8 baboons. Blood, endometriotic lesions, and eutopic endometrial samples were collected from women undergoing laparoscopy for surgical removal of endometriosis. Blood was also collected from control participants with no signs and symptoms associated with the disease as well as from baboons prior to, and then 1, 3, 6, 9, and 15 months postinduction of endometriosis. MicroRNA-451a was assessed by quantitative real-time polymerase chain reaction in all samples. In humans, serum miR-451a levels positively correlated with endometriotic lesion miR-451a content, and sera levels were significantly higher in these participants compared to controls. The area under the curve (AUC) for miR-451a was 0.8599. In baboons, serum miR-451a reached statistically significant peak levels at 6 months postinduction of endometriosis. We conclude from this study that sera miR-451a levels positively correlated with endometriotic lesion content and are significantly greater compared to sera levels in women without visible signs or symptoms of endometriosis. MicroRNA-451a may serve as a serum diagnostic marker for endometriosis.
Reprod Sci. 2017 Aug;24(8):1187-1194.
Smad3/4 Binding to Promoter II of P450arom So As to Regulate Aromatase Expression in Endometriosis.
Activin A can stimulate aromatase P450 (P450arom) expression in eutopic endometrial stromal cells (ESCs) of endometriosis by activin type I receptor-Smad pathway. In order to identify Smad3/4 binding to P450arom promoter II that mediates activin A response in ESCs, polymerase chain reaction (PCR) products of a serial truncated deletion of the P450arom promoter II region between -904 and +87 bp were inserted into the pGL3-basic vector to generate the promoter reporter plasmids. Luciferase reporter plasmids were cotransfected into cells with or without activin A (25 ng/mL). The pGL3 -705/+87 revealed a luciferase activity similar to pGL3 -904/+87, whereas progressive truncation to position -464/+87 and -192/+87, the luciferase activity was significant variation. Chromatin immunoprecipitation assay and Smad4-small interfering RNA (siRNA) testify that Smad3/4 binds to the activin A-responsive aromatase promoter in ESCs. Chromatin immunoprecipitation assay-PCR assay demonstrated anti-Smad3 antibody complexes could interact with the amplified DNA of the activin A-responsive P450arom promoter. Mutations of the binding site (-141/-138 bp, -165/-162 bp) in P450arom promoter II significantly reduced promoter activity of activin A fold-induction to 26% and 28%, respectively. We cotransfected pGL3 -705/+87 with control siRNA and Smad4-siRNA into ESCs in the presence of activin A. Luciferase analysis showed that Smad4-siRNA abolished increased promoter activity of activin A-induced P450arom expression. The effect of activin A on the p-Smad3 accumulation in the cytoplasm and nucleus was significantly abrogated following the pretreatment of ESCs with Smad4-siRNA. In conclusion, activated Smad3 proteins can bind to P450arom promoter -705/+87 bp region, responsive to activin A in ESCs, which can promote P450arom transcription.
Radiol Case Rep. 2016 Sep 27;11(4):303-308.
Subcapsular hepatic endometriosis: case report and review of the literature.
Hepatic endometriosis is a very rare medical condition characterized by the implantation of ectopic endometrial tissue within the hepatic parenchyma. Preoperative diagnosis is difficult via cross-sectional imaging and histopathologic evaluation remains the gold standard for diagnosis. We report a case of hepatic endometrioma in a 44-year-old woman with history of endometriosis. The literature is reviewed, and magnetic resonance imaging findings together with differential diagnosis of hepatic endometriosis are highlighted.
Eur Radiol. 2017 Jul;27(7):2765-2775.
European society of urogenital radiology (ESUR) guidelines: MR imaging of pelvic endometriosis.
Endometriosis is a common gynaecological condition of unknown aetiology that primarily affects women of reproductive age. The accepted first-line imaging modality is pelvic ultrasound. However, magnetic resonance imaging (MRI) is increasingly performed as an additional investigation in complex cases and for surgical planning. There is currently no international consensus regarding patient preparation, MRI protocols or reporting criteria. Our aim was to develop clinical guidelines for MRI evaluation of pelvic endometriosis based on literature evidence and consensus expert opinion. This work was performed by a group of radiologists from the European Society of Urogenital Radiology (ESUR), experts in gynaecological imaging and a gynaecologist expert in methodology. The group discussed indications for MRI, technical requirements, patient preparation, MRI protocols and criteria for the diagnosis of pelvic endometriosis on MRI. The expert panel proposed a final recommendation for each criterion using Oxford Centre for Evidence Based Medicine (OCEBM) 2011 levels of evidence.
- This report provides guidelines for MRI in endometriosis. • Minimal and optimal MRI acquisition protocols are provided. • Recommendations are proposed for patient preparation, best MRI sequences and reporting criteria.
J Clin Pharmacol. 2017 May;57(5):640-651.
Model-Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of EndometriosisSymptoms.
Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation.
Semin Reprod Med. 2017 Jan;35(1):81-87.
Management of Endometriosis Involving the Urinary Tract.
Endometriosis is a common cause of infertility and disabling pelvic pain in reproductive age women. The most widely accepted theory of its pathogenesis is the retrograde flow of menstrual products, although extra-abdominal and extrapelvic diagnoses have been made. After the pelvic peritoneum and gynecologic structures, the most commonly affected sites are the lower gastrointestinal and urinary tracts. When the urinary tract is involved, the bladder is the predominant site, followed by the ureters. The focus of this seminar will thus be these two anatomic sites. Delayed diagnosis is unfortunately common for endometriosis as a whole, but more so when extrapelvic sites are involved. While the first-line therapy for endometriosis is medical management, urinary tract involvement often represents advanced stage of the disease, thereby requiring surgical intervention. With timely diagnosis and intervention by skilled gynecologic or urologic surgeons, favorable outcomes can be attained.
Semin Reprod Med. 2017 Jan;35(1):25-30.
Management of Endometriomas.
Ovarian endometriomas affect 17 to 44% of women with endometriosis, and are often associated with pelvic pain and infertility. Treatment options include expectant management, medical and/or surgical treatment, and in vitro fertilization and embryo transfer (IVF-ET). The choice of treatment depends mostly on the associated symptoms. In most cases, surgery is the preferred choice, since endometriomas do not respond to medical treatment, which may only treat associated pain. In case of infertility, IVF-ET may be a suitable alternative to surgery, particularly when there is no associated pain. According to the best available scientific evidence, laparoscopic excision of the endometrioma wall should be considered the procedure of choice. Concerns have been raised as to the possibility that surgical excision may damage the ovarian reserve, but recent evidences demonstrate that part of the damage may be due to the presence of the endometrioma itself. Indication to surgical treatment should balance the possible risks of damaging the ovarian reserve with the advantages of surgery in terms of satisfactory pain relief rates and pregnancy rates, and of obtaining tissue specimen for ruling out the rare cases of unexpected ovarian malignancy. A score system to guide the clinician in the decision to perform or withhold surgery is presented.
Semin Reprod Med. 2017 Jan;35(1):31-37.
Management of Endometriosis in the Infertile Patient.
The management of endometriosis-related infertility remains debated. However, in recent years, the role of in vitro fertilization (IVF) has progressively grown. Reasons to explain this change include (1) the improvement of the effectiveness and safety of IVF, (2) the raised awareness of the modest effectiveness of surgery, (3) the inherent risks of surgery including in particular the damage to the ovarian reserve when ovarian endometriomas have to be removed, (4) the ineffectiveness of intrauterine insemination and the possible risks of endometriosisprogression associated with the use of this technique. However, IVF is not able to overcome all the potential detrimental effects of endometriosis and can actually fail. Future efforts should aim at improving the effectiveness and safety of both surgery and IVF. Fertility preservation techniques may play a role in the future, but data are currently too scanty to support its recommendation.
J Obstet Gynaecol Res. 2017 Jan;43(1):135-139.
Prevalence of high-risk human papillomavirus infection in women with ovarian endometriosis.
In this study, we aimed to determine the prevalence of human papillomavirus (HPV) in ovarian endometriosis and ovarian tissue from women without endometriosis. Understanding the pathogenesis of the disease could help us design preventative strategies as well as novel and appropriate treatment approaches in this regard.
In this cross-sectional study, formalin-fixed and paraffin-embedded tissue sections from 50 and 49 ovaries with and without endometriosis, respectively, were evaluated for the presence of high-risk HPV using the polymerase chain reaction technique. Prevalence of HPV infection and other related characteristics of the studied population were compared.
High-risk HPV infection was detected in 13 (26%) and five (10.2%) of the samples with and without endometriosis, respectively (P = 0.041, χ2 = 3.16). Mean age and parity were not significantly different in subjects with and without HPV infection in the two studied groups (P = 0.7 and P = 0.06 for age in case and control groups, respectively; and P = 0.32 and P = 0.09 for parity in case and control groups, respectively).
The results of our study indicated a higher rate of high-risk HPV infection among patients with endometriosis. The findings could provide us baseline information for future studies regarding the pathogenesis of endometriosis and the role of viral infection and their possible impact on future cancer development in this group of patients.
J Minim Invasive Gynecol. 2017 Feb;24(2):203-204.
Ten Principles for Safe Surgical Treatment of Ovarian Endometriosis.
To show a step-by-step laparoscopic approach for excision of an ovarian endometrioma following surgical principles for safety and maximal preservation of ovarian function.
Video. Medical management of ovarian endometriomas is not recommended. Operative laparoscopy is the treatment of choice. Although considered a simple procedure, ovarian cystectomy requires a precise and correct technique in order to preserve ovarian function.
A private hospital.
An asymptomatic, 27-year-old woman with ultrasound imaging suggesting a 6.2 × 5.4 cm left endometrioma. Additional findings of endometriotic implants were noted in the posterior aspect of the left broad ligament, retrocervical region, Douglas pouch, and left round ligament.
After trocar insertion, standard inspection of the pelvic cavity with identification of endometriosis lesions and adhesions was performed. The endometrioma was drained with direct trocar puncture to avoid spillage of the endometriotic contents. Cyst aspiration and saline cleaning were executed. After drainage, a cold cut was performed at the puncture site for better identification of the cyst capsule. Through gentle traction and countertraction, the capsule was peeled from the ovarian cortex, preserving as much ovarian tissue as possible followed by careful hemostasis with a bipolar instrument. The ovary is fixed, anatomy re-established, and concomitant pelvic endometriosis resected. We aim for complete surgical excision in order to avoid leaving disease behind. The ovarian edges were reapproximated using simple interrupted stitches.
MEASUREMENTS AND MAIN RESULTS:
The total procedure time was 40 minutes.
Laparoscopic endometrioma stripping offers an effective option for ovarian endometriosistreatment, reducing recurrence and being reproducible by gynecologic surgeons after proper training.
J Evid Based Complementary Altern Med. 2016 Dec 8
Treatment of Recurrent Ovarian Cysts and Primary Infertility by Iranian Traditional Medicine: A Case Report.
Infertility is a medical and psychosocial problem with a high prevalence. There are different treatments for this problem in Iranian traditional medicine. A 28-year-old woman presented with the complaints of 4 emergency operations of the left ovarian cyst during 4 years and infertility. Diagnostic laparoscopy showed an ovarian cyst, adhesion, and endometriosis. Hysteroscopy was unremarkable. After 2 months of letrozole administration, the ovarian cyst ruptured again. Considering the failure of conventional treatments, Iranian traditional medicine products were administered to the patient. After 3 months, the patient conceived and delivered a healthy boy through normal vaginal delivery. These compounds may help with pregnancy as a uterine tonic, vitalizer, and aphrodisiac with brain and cardiac tonic properties.
Int J Womens Health. 2016 Nov 28;8:677-682
Effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women.
Angiogenesis has been found to be among the most important factors in the pathogenesis of endometriosis. The formation of new blood vessels is critical for the survival of newly implanted endometriotic foci. The use of 3-D power Doppler allows for the demonstration of the dynamic vascular changes that occur during the process of in vitro fertilization (IVF). We aimed to evaluate the effect of ovarian endometrioma on uterine and ovarian blood flow in infertile women.
MATERIALS AND METHODS:
In a case-control study at a university teaching hospital, 138 women with unilateral ovarian endometrioma scheduled for IVF were compared to 138 women with male-factor or unexplained infertility. In the mid-luteal (peri-implantation) phase of the cycle, endometrial thickness, uterine and ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, 3-D power Doppler vascularization index (VI), flow index (FI), and vascularization FI (VFI) values were measured in both groups.
There were no significant differences (P>0.05) in endometrial thickness, uterine ovarian artery pulsatility index and resistance index, endometrial and ovarian volume, or VI, FI, and VFI between the two groups. Furthermore, the endometrial and ovarian Doppler indices were not influenced by endometrioma size. No significant differences were observed in the ovarian Doppler indices between endometrioma-containing ovaries and contralateral ovaries.
Ovarian endometrioma is not associated with impaired endometrial and ovarian blood flows in infertile women scheduled for IVF, and it is not likely to affect endometrial receptivity or ovarian function through a vascular mechanism.
Fertil Steril. 2017 Feb;107(2):439-447.
Estrogen stabilizes hypoxia-inducible factor 1α through G protein-coupled estrogen receptor 1 in eutopic endometrium of endometriosis.
To investigate whether G protein-coupled estrogen receptor (GPER, also known as GPR30 and GPER1) stabilizes hypoxia-inducible factor 1α (HIF-1α) in eutopic endometrium (EuEM) of endometriosis.
Immunohistochemical analysis and experimental in vitro study.
Patients with or without endometriosis.
The EuEM and normal control endometrium (CoEM) were obtained by curettage. Primary cultured endometrial stromal cells (ESCs) were treated with 17β-E2, G1, or G15.
MAIN OUTCOME MEASURE(S):
The EuEM and CoEM were collected for immunohistochemistry. Western blot, polymerase chain reaction, ELISA, and dual luciferase experiments were used to detect expression of GPER, HIF-1α, vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP9) in ESCs. Estradiol and G1 were used as agonists of GPER, G15 as an antagonist. Migration of ESCs and endothelial tube formation of human umbilical vein endothelial cells cultured in medium collected from ESCs were measured.
Protein levels of GPER and HIF-1α were higher in EuEM than in CoEM. Protein levels of HIF-1α but not HIF-1α mRNA levels increased concurrently with GPER after E2 and G1 treatment. Furthermore, expression and activity of VEGF and MMP9 increased under E2 and G1 stimulation. However, these effects disappeared when GPER was blocked.
G protein-coupled estrogen receptor stabilizes HIF-1α and thus promotes HIF-1α-induced VEGF and MMP9 in ESCs, which play critical roles in endometriosis.
Niger Med J. 2016 Nov-Dec;57(6):329-333.
Abdominal wall endometrioma: Our experience in Vladimir, Russia.
Endometriosis is defined as an estrogen-dependent, benign inflammatory disease characterized by the presence of ectopic endometrial implants. Abdominal wall endometrioma (AWE) being a rare entity is a benign tumor defined as ectopic functional, endometrial tissue located in the abdominal wall.
SUBJECTS AND METHODS:
A retrospective study of 23 female patients treated with AWE in four departments of three centers in Vladimir city, Russia, from January 2010 to December 2014 was performed.
In twenty patients (87%), AWE was symptomatic, and in three patients (13%), AWE was asymptomatic. Esquivel triad presented in 17 patients (74%), and modified Esquivel triad existed in 20 patients (87%). All 23 patients were operated, and AWE excision was performed. Recurrence occurred in 4 cases (17.4%) and was associated with postoperative pain and seroma.
Postoperative pain for more than 7 days and seroma (on ultrasonography) seem to be associated with recurrence of AWE.
Semin Reprod Med. 2017 Jan;35(1):65-71.
Strategies for Management of Colorectal Endometriosis.
Endometriosis has clearly three distinct clinical presentations and deep endometriosis, especially compromising the rectosigmoid is probably the most concerning one for both patients and surgeons. Currently, with the available tools, it is mandatory to have a precise diagnostic of this type of disease prior to indication of treatment. Strategies to manage this form of endometriosis will take into account several involved aspects, such as age of the patient, reproductive desire or infertility, clinical symptoms, as well as the extension and localization of the disease. Treatment could vary from more conservative to more radical depending on those aspects. As we pointed out in this article, the key to manage colorectal endometriosis is to start with a good diagnosis. Knowing exactly what is the extension and localization of the disease and knowing the patient’s wishes as well as the clinical complaints, surgeons are able to define the best option for each patient. Critical points should always be discussed; for example, patients chosen to have clinical treatment should be aware of important issues regarding the follow-up, while patients undergoing surgery must be advised about all surgical possibilities and related complications.
Semin Reprod Med. 2017 Jan;35(1):72-80.
Nerve Sparing and Surgery for Deep Infiltrating Endometriosis: Pessimism of the Intellect or Optimism of the Will.
Nerve-sparing surgery is an emerging technique for surgery-related dysfunction. Within the past 15 years, an essential progress in recognition and understanding of the anatomy of the pelvic autonomous nervous system has been made. Surgical preservation of vegetative nerves has become well known in many cancer centers. The technique has led to improvement of the quality of life following oncologic radical procedures. Positive results have led to the adoption of such techniques in the surgical treatment of deep infiltrating endometriosis in an aim to prevent urinary, rectal, and sexual dysfunction. Even though nerve-sparing excision of endometriosis is feasible and offers good outcomes in terms of bladder morbidity; digestive and sexual functions seem to be more complex to assess. Moreover, functional impairment in deep infiltrating endometriosis may preexist prior to surgery and function may not be restored despite nerve preservation. In cases where endometriosis lesions are deeply embedded in the parametrium, nerve-sparing techniques may only be feasible in those with a unilateral involvement. The nerve-sparing surgical approach is therefore a safer radical surgery in the hands of experienced surgeons that has to be tailored to the unique nature of deep infiltrating endometriosis and balanced between the natural aggressiveness of such a debilitating disease and postoperative morbidity. Good knowledge of pelvic nerve anatomy and function allows understanding of related symptoms to reduce morbidity, whenever this goal is still achievable.
Mol Med Rep. 2017 Jan;15(1):249-255.
MicroRNA expression profiles and networks in CXCL12‑stimulated human endometrial stromal cells.
The chemokine stromal cell-derived factor-1 (C-X-C motif chemokine ligand 12; CXCL12) is important in the recruitment of leukocytes to the peritoneal cavity and the regulation of endometriotic tissue growth in endometriosis patients. However, the alterations in microRNA (miRNA) expression induced by CXCL12 remain to be fully elucidated. The present study evaluated key miRNAs in CXCL12‑stimulated endometrial stromal cells (ESCs), and investigated the underlying cellular regulatory mechanisms of CXCL12 in endometriosis by building networks between miRNAs, genes and gene ontologies (GOs). Differential expression of miRNAs and mRNAs induced by CXCL12 stimulation in ESCs was measured using miRNA and gene chips, and it was observed that 35 miRNAs and 1,671 mRNAs were differentially expressed. Using potential target genes of the 35 miRNAs, intersections of these genes were examined and 63 intersection genes were identified. A total of 39 GOs were obtained for these intersection genes, based on information from GO databases, including immune cell chemoattractants, inflammatory and immune responses, and pathological processes of endometriotic lesions in endometriosis. In addition, miRNA‑gene networks were built according to the GO and Kyoto Encyclopedia of Genes and Genomes databases. The present study, to the best of our knowledge, provides the most complete miRNAome and mRNAome profiles, and the most detailed investigation of the underlying cellular regulatory mechanisms, of the effects of CXCL12 in endometriosis. These results may facilitate the complete elucidation of the role of CXCL12 in endometriosis, and its underlying epigenetic mechanisms.
Reproduction. 2017 Mar;153(3):277-284.
Selenium-Binding Protein 1 (SBP1) autoantibodies in ovarian disorders and ovarian cancer.
Infertility is a risk factor for ovarian cancer (OvCa). The goal was to determine if antibodies to selenium-binding protein 1 (SBP1), an autoantibody we identified in patients with premature ovarian failure (POF), occurs in both infertility and OvCa patients, and thus could be associated with preneoplasia. Anti-SBP1 was measured by immunoassay against recombinant SBP1, in sera from OvCa (n = 41), infertility (n = 92) and control (n = 87) patients. Infertility causes were POF, unexplained, irregular ovulation or endometriosis. The percent of anti-SBP1-positive sera was higher in POF (P = 0.02), irregular ovulation (P = 0.001), unexplained causes (P = 0.02), late (III-IV)-stage OvCa (P = 0.02) but was not significant in endometriosis, benign ovarian tumors/cysts, early stage (I-II) OvCa or uterine cancer compared to healthy controls. Anti-SBP1 was significantly higher in women with serous (P = 0.04) but not non-serous (P = 0.33) OvCa compared to controls. Also, we determined if anti-SBP1 was associated with CA125 or anti-TP53, markers often studied in OvCa. Anti-TP53 and CA125 were measured by established immunoassays. The ability of anti-SBP1 alone to discriminate infertility or OvCa from controls or when combined with anti-TP53 and CA125, to identify OvCa was evaluated by comparing the area under the curve (AUC) in ROC analysis. Anti-SBP1 alone discriminated infertility (AUC = 0.7; P = 0.001) or OvCa (AUC = 0.67; P = 0.03) from controls. The sensitivity and specificity of OvCa identification was increased by combining CA125, anti-TP53 and anti-SBP1 (AUC = 0.96). Therefore, anti-SBP1 occurs in infertile women with POF, ovulatory disturbances or unexplained infertility and in serous OvCa. This suggests an autoimmune process is associated with the development of serous OvCa.
J Med Life. 2016 Jan-Mar;9(1):39-45.
The etiopathogenesis of uterine fibromatosis.
Uterine fibroids or uterine leiomyomas are the most common benign tumors of the uterus among women of fertile age, while the etiology is still incompletely elucidated. The occurrence and development of the fibromatosis may be related to certain risk factors and genic mechanisms, although the exact causes are not yet fully known. The development of uterine fibroids is correlated not only with the metabolism and with the level of female sexual hormones, estrogen, and progesterone, but also with the number of these hormone receptors expressed on the surface of the myometrium. Proliferative effects of estrogen and progesterone may be exercised through proinflammatory factors (TNF alpha), growth factors (IGF1, IGF2, TGFbeta3 and betaFGF) or inhibitors of apoptosis (p53 suppression). A number of predisposing factors such as ethnicity – black skin, early menarche, nulliparity, caffeine and alcohol, chronic inflammation, obesity, were also identified. Approximately 40% of the uterine fibroids are caused by the same cytogenetic alterations found in the other tumor types such as kidney, lung, or leiomyosarcoma. As part of a system dysfunction, uterine fibromatosis was connected to other disorders such as AHT (arterial hypertension), endometrium adenocarcinoma, adenomyosis, endometriosis, diabetes mellitus, breast tumors, seemingly with a common causality. The action and effect of some hormonal imbalances over the various organs depend on the histological and local expression particularities of the various receptors, being the cause for many disorders, among which the uterine fibromatosis, coexisting or accompanying the later. This article examines and summarizes the latest data refreshed literature etiopathogenesis offering indicators of uterine fibroids.
Am J Reprod Immunol. 2017 Jan;77(1)
Effects of TSLP on obstetrical and gynecological diseases.
Thymic stromal lymphopoietin (TSLP) is produced mainly by epithelial cells and was originally found to stimulate the growth and activation of B cells, but it is now shown to function on both hematopoietic and non-hematopoietic cell lineages. Despite a number of studies focusing on the role of TSLP in Th2 response for allergic disorders, it is becoming increasingly evident that TSLP may also be involved in multiple other disease states. This review will focus on recent advances on the effects of TSLP on obstetrical and gynecological diseases, including pregnancy failure, endometriosis, and cervical cancer.
Radiologia. 2017 Mar – Apr;59(2):115-127.
Gynecological pelvic pain as emergency pathology.
Acute pelvic pain is a common condition in emergency. The sources of acute pelvic pain are multifactorial, so it is important to be familiar with this type of pathologies. The purpose of this article is review the main causes of gynecological acute pelvic pain and their radiologic appearances to be able to make an accurate diagnosis and provide objective criteria for patient management.
Hum Reprod Update. 2017 Mar 1;23(2):166-187.
Implications of telomeres and telomerase in endometrial pathology.
Eukaryotic chromosomal ends are linear and are protected by nucleoprotein complexes known as telomeres. The complex structural anatomy and the diverse functions of telomeres as well as the unique reverse transcriptase enzyme, telomerase that maintains telomeres are under intensive scientific scrutiny. Both are involved in many human diseases including cancer, but also in ageing and chronic disease such as diabetes. Their intricate involvement in many cellular processes and pathways is being dynamically deciphered in many organs including the endometrium. This review summarizes our current knowledge on the topic of telomeres and telomerase and their potential role in providing plausible explanations for endometrial aberrations related to common gynaecological pathologies.
OBJECTIVE AND RATIONALE:
This review outlines the recent major findings in telomere and telomerase functions in the context of endometrial biology. It highlights the contemporary discoveries in hormonal regulation, normal endometrial regeneration, stem cells and common gynaecological diseases such as endometriosis, infertility, recurrent reproductive failure and endometrial cancer (EC).
The authors carried out systematic PubMed (Medline) and Ovid searches using the key words: telomerase, telomeres, telomere length, human telomerase reverse transcriptase, telomeric RNA component, with endometrium, hormonal regulation, endometrial stem/progenitor cells, endometrial regeneration, endometriosis, recurrent miscarriage, infertility, endometrial hyperplasia, EC and uterine cancer. Publications used in this review date from 1995 until 31st June 2016.
The human endometrium is a unique somatic organ, which displays dynamic telomerase activity (TA) related to the menstrual cycle. Telomerase is implicated in almost all endometrial pathologies and appears to be crucial to endometrial stem cells. In particular, it is vital for normal endometrial regeneration, providing a distinct route to formulate possible curative, non-hormonal therapies to treat chronic endometrial conditions. Furthermore, our current understanding of telomere maintenance in EC is incomplete. Data derived from other malignancies on the role of telomerase in carcinogenesis cannot be extrapolated to EC because unlike in other cancers, TA is already present in proliferating healthy endometrial cells.
Since telomerase is pivotal to endometrial regeneration, further studies elucidating the role of telomeres, telomerase, their associated proteins and their regulation in normal endometrial regeneration as well as their role in endometrial pathologies are essential. This approach may allow future development of novel treatment strategies that are not only non-hormonal but also potentially curative.
J UOEH. 2016;38(4):271-278.
Immunohistochemical Analysis of the Effect of Dienogest on Ovarian Endometriotic Cysts.
Dienogest is a novel progestin with potent oral progestational activity that inhibits the clinical symptoms of endometriosis. We herein evaluated the effect of dienogest on ovarian endometriotic cysts via immunohistochemistry. Ovarian endometriotic cyst specimens were collected from 12 patients treated with dienogest and 20 patients not treated with hormones (controls). The expression of estrogen receptor (ER)-α, progesterone receptor A (PRA), and Ki-67 was studied by immunohistochemistry. As compared with the controls, the cell proliferation index was significantly reduced in both epithelial and stromal cells of the endometriotic cysts following the use of dienogest (P = 0.022 and P = 0.004, respectively). However, there was no significant difference between endometriotic cysts with and without the use of dienogest in the expressions of ER-α and PRA in the epithelial and stromal cells. Irrespective of the use of dienogest, the expression levels of ER-α and PRA in the epithelial cells were low (median: 32% and 8%, respectively). Conversely, the expression levels of ER-α and PRA in the stromal cells were well preserved (median: 68% and 92%, respectively). In the controls, there was no significant difference between endometriotic cysts in the expression levels of Ki-67, ER-α and PRA in epithelial and stromal cells during the proliferative and secretory phases. The finding of a reduction in the cell proliferation index by the use of dienogest with no change in the expressions of hormonal receptors may not support the direct progestational effect of dienogest on ovarian endometriotic cysts.
Genom Data. 2016 Nov 29;11:55-59.
Common variation of the CYP17 gene in Iraqi women with endometriosisdisease.
Common variants among genes coding for enzymes in sex steroid biosynthetic pathways may influence the risk of endometriosis in Iraqi women patients in the last years. Cytochrome P450c17a1 (CYP17), a gene that codes for a key enzyme (cytochrome P450c17a1) in a rate-limiting step of estrogen biosynthesis has attracted considerable attention as an important gene for endometriosis. To evaluate the relationship between common genetic variations in CYP17 and endometriosis risk and determine the main effects of those variations on the gene expression. A women-based case control study of Iraqi women aged range (23-46), the associations between selected single-nucleotide polymorphisms (SNPs) in the CYP17 gene and endometriosis diagnosis in fifty women and thirty disease-free controls were evaluated. The study found a significant association (P ≤ 0.01)between endometriosis and selected SNPs of CYP17 gene, with the homozygous genotype conferring decreased risk. A highly significant difference (P ≤ 0.01) in CYP17 gene expression from women with versus without endometriosis and increased by 1.56-fold in women with endometriosis. These findings suggest that variation in or around CYP17 may be associated with endometriosis development in the Iraqi women.
Med Ultrason. 2016 Dec 5;18(4):469-474.
Diagnosis of endometriotic lesions by sonovaginography with ultrasound gel.
The aim of the study was to evaluate the diagnostic ability of sonovaginography (SVG) with ultrasound gel in patients with endometriosis.
MATERIAL AND METHODS:
We conducted a multicentre prospective study, which included 193 patients with symptoms highly suggestive for endometriosis. All patients were investigated by transvaginal sonography and SVG with gel and afterwards underwent laparoscopic surgery. For each category of endometriotic lesions investigated, we calculated and compared the sensitivity, specificity, positive predictive value and negative predictive value of the imagisticinvestigations used.
In the case of endometriotic lesions of the uterosacral ligaments, SVG with gel had a sensitivity of 78.5% and a specificity of 96% (p=ns). The lesions of the vagina and rectovaginal septum were diagnosed with a sensitivity of 79%, respectively 94% (p=ns), obtaining a specificity of 99%, respectively of 97% (p=0.007). The lesions of the Douglas pouch were identified with a sensitivity of 81% (p=0.015), and those of the rectosigmoid with a 94% sensitivity (p=0.010). We obtained lower sensitivity (67%) in detecting the lesions of the urinary bladder (p=ns).
SGV with ultrasound gel represents a useful investigation tool for the evaluation of endometriotic lesions in the posterior pelvic compartment.
Eur J Obstet Gynecol Reprod Biol. 2017 Mar;210:94-101.
Laparoscopic management of ureteral endometriosis: A systematic review.
The optimal management of ureteral endometriosis (UE) is not yet well defined. The choice on surgical approach and type of procedure has been based both on surgeons’ experience and the location and depth of the lesion. The aim of this study was to review evidence about laparoscopic management of ureteral endometriosis, including preoperative evaluation, surgical details and postoperative follow-up. PubMed Central and SCOPUS databases were searched to identify studies reporting cases of laparoscopically managed ureteral endometriosisand including data regarding preoperative findings, surgical interventions and postoperative follow-up. Two sets of MeSH terms were used: 1) “laparoscopy”, “endometriosis” and “ureter”; 2) “laparoscopy”, “endometriosis” and “urinary tract”. Databases were searched for articles published since 1996, in English, French, Spanish and Portuguese, without restrictions regarding study design. Studies reporting surgical approaches other than conventional laparoscopy were excluded, as were case reports and case studies including fewer than 5 cases. From 327 studies obtained through database searching, 18 articles were finally included in this review, including a total of 700 patients with ureteral endometriosis. 57% of patients had at least one previous surgery for endometriosis. Preoperative evidence of significant hydroureter/hydronephrosis was found in 324 of 671 (48.3%) patients. Dysmenorrhea (81.4%), pelvic pain (70.2%) and dyspareunia (66.4%) were the presenting symptoms more commonly reported by the patients. Most patients presented no symptoms specific to the urinary tract. Ureteral endometriosis was more frequent in the left ureter (53.6%) and it was bilateral in 10.6% of cases. Ureterolysis alone was considered a sufficient procedure in 579 of 668 patients (86.7%), and in the remaining 89 patients ureteral resection was necessary. Rectovaginal and uterosacral involvement was present in 58.8% and 47.9% of patients, respectively. Concomitant ureteral and bladder endometriosis was described in 19.8% of patients. Only 6 studies reported cases of accidental ureteral injuries, in 1-24% of patients. Cases of conversion to laparotomy are reported in only 6 studies, in 3-6,7% of patients. Major postoperative complications occurred in 21 out of 682 patients (3.2%). The need for reoperation during follow-up period because of ureteral endometriosispersistence or recurrence was 3.9%. When performed in specialized centers, laparoscopic ureterolysis showed to be a feasible and safe procedure, with a low risk of complications and with satisfactory long-term results. This conservative approach may be used as the initial treatment option in most patients with ureteral endometriosis.
Hum Reprod. 2017 Feb;32(2):332-339.
mRNA levels of low-density lipoprotein receptors are overexpressed in the foci of deep bowel endometriosis.
Is mRNA expression of LDL receptors altered in deep bowel endometriotic foci? SUMMARY ANSWER: mRNA expression of LDL receptors is up-regulated in deep bowel endometriotic foci of patients with endometriosis.
WHAT IS KNOWN ALREADY:
Several studies have demonstrated the overexpression of low-density lipoprotein receptors in various tumour cell lines and endometriosis has similar aspects to cancer, mainly concerning the pathogenesis of both diseases. This is the first study we know of to investigate lipoprotein receptors expression in deep endometriosis with bowel involvement.
STUDY DESIGN, SIZE, DURATION:
During 2014-2015, an exploratory case-control study was conducted with 39 patients, including 20 women with a histological diagnosis of deep endometriosis compromising the bowel and 19 women without endometriosis who underwent laparoscopic tubal ligation.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Peripheral blood samples were collected on the day of surgery for lipid profile analysis, and samples of endometrial tissue and of bowel endometriotic lesions were also collected. The tissue samples were sent for histopathological analysis and for LDL-R and LRP-1 gene expression screening using quantitative real-time PCR.
MAIN RESULTS AND THE ROLE OF CHANCE:
Patients with deep endometriosis had lower LDL-cholesterol than patients without the disease (119 ± 23 versus 156 ± 35; P = 0.001). Gene expression analysis of LDL receptors revealed that LDL-R was more highly expressed in endometriotic lesions when compared to the endometrium of the same patient but not more than in the endometrium of women without endometriosis (0.027 ± 0.022 versus 0.012 ± 0.009 versus 0.019 ± 0.01, respectively; P < 0.001). LRP-1 was more highly expressed in endometriotic lesions, both when compared with the endometrium of the same patient and when compared with the endometrium of patients without the disease (0.307 ± 0.207 versus 0.089 ± 0.076 and versus 0.126 ± 0.072, respectively; P < 0.001). The study also showed that LDL-R gene expression in the endometrium of women with endometriosis was higher during the secretory phase of the menstrual cycle (P = 0.001). LRP-1 gene expression was increased during the secretory phase in the endometrium of women without the disease (P = 0.008).
LIMITATIONS, REASONS FOR CAUTION:
In the endometriotic lesions, the presence of fibrosis is substantial, restricting access to the stromal and glandular components of the lesion. Despite that, we found that LDL receptor mRNA was overexpressed. Future studies may perform laser microdissection to isolate the area of interest in the target tissue, excluding fibrosis contamination.
WIDER IMPLICATIONS OF THE FINDINGS:
This study supports the feasibility of LDL-R targeted therapy in the treatment of deep endometriosis.
STUDY FUNDING/COMPETING INTERESTS:
This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2011/17245-0). The authors have no conflicts of interest to declare.
Med Sci Monit. 2016 Dec 17;22:4960-4966.
Effects of Vitamin D on Endometriosis-Related Pain: A Double-Blind Clinical Trial.
BACKGROUND Endometriosis is a disabling disease of reproductive-age women. Dysmenorrhea, dyspareunia, and pelvic pain are the main symptoms of endometriosis. Its etiology is not clear. Endometriosis may have various causes, including vitamin D deficiency, but its effect is controversial. MATERIAL AND METHODS In this double-blind clinical trial, we enrolled patients with endometriosis diagnosed and treated by laparoscopy, with scores of at least 3 for of dysmenorrhea and/or pelvic pain at 8 weeks after surgical treatment. They were randomly prescribed vitamin D (50 000 IU weekly for 12 weeks) or placebo. Severity of pain in the 2 groups (placebo and treatment) was compared by VAS test at 24 weeks after surgical treatment. RESULTS There were 19 patients in the vitamin D group and 20 in the placebo group. Baseline characteristics in the 2 groups were similar. Following the treatment with vitamin D or placebo, we did not find significant differences in severity of pelvic pain (p=0.24) and dysmenorrhea (p=0.45) between the 2 groups. Mean pelvic pain at 24 weeks after laparoscopy in the vitamin D group was 0.84±1.74 and in placebo group it was 0.68±1.70 (p=0.513). Mean dysmenorrhea was 2.10±2.33 in the vitamin D group and 2.73±2.84 in the placebo group (p=0.45). CONCLUSIONS After ablative surgery for endometriosis, vitamin D treatment did not have a significant effect in reducing dysmenorrhea and/or pelvic pain.
J Obstet Gynaecol Res. 2017 Feb;43(2):308-319.
Effect of interleukin-1β and lipoxin A4 in human endometriotic stromal cells: Proteomic analysis.
Lipoxin A4 (LXA4 ) can function as an endogenous ‘breaking signal’ in inflammation and plays an important role in the progression of endometriosis. The proteome responses to interleukin-1β (IL-1β) or LXA4 in human endometriotic stromal cells (ESC) are not well understood.
In this study, primary ESC were cultured from ovarian endometriosis tissue. Three groups were established: the control group; the IL-1β stimulation group; and the IL-1β and LXA4 incubation group. Proteins were assessed on 2-D polyacrylamide gel electrophoresis (2D-PAGE), and differentially expressed protein spots were further identified on matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MALDI-TOF-MS). Wound healing and transwell assays were performed to assess the migration and invasion of ESC after treatment.
In total, 40 differentially expressed protein spots were identified successfully on MALDI-TOF-MS. The proteins identified were related to cell structure, metabolism, signal transduction, protein synthesis and membrane structure, processes that may be involved in the development of endometriosis. Vinculin and IL-4 were further analyzed on western blot and quantitative real-time polymerase chain reaction. Moreover, LXA4could suppress the migration and invasion of ESC induced by IL-1β.
LXA4 may inhibit the progression of endometriosis partly by lowering or raising the effect of IL-1β, mediated via some inflammation-related proteins (e.g. vinculin) and immune response-related protein (e.g. IL-4) in vitro.
Eur J Obstet Gynecol Reprod Biol. 2017 Mar;210:102-107.
Diagnostic accuracy of Cancer Antigen 125 (CA125) for endometriosis in symptomatic women: A multi-center study.
To assess the diagnostic accuracy of serum Cancer Antigen 125 (CA 125)≥30units/milliliter (u/ml) for diagnosing endometriosis in symptomatic women.
Prospective observational cohort study including patients with symptoms of pelvic pain or subfertility undergoing elective diagnostic laparoscopy at two tertiary referral hospitals. We excluded patients suspected to have other gynecological pathology. We evaluated the accuracy of serum CA 125 (index test) with histologically confirmed endometriosis (reference standard).
Fifty-eight consecutive women recruited between October 2013 to March 2015. Women with endometriosis had a higher CA 125 level than those without endometriosis (mean 54.7+/-71.6 vs 16.2+/- 8.0). The specificity of CA 125≥30u/ml was 96% (95% CI 81.7-99.9%) and sensitivity was 57% (95% CI 37.4-74.5%). The positive likelihood ratio for the histological presence of endometriosis with a CA 125≥30u/ml was 15.8 (95% CI 2.3-112) providing a post-test probability of 94% (95% CI 71%-99%) in women with pelvic pain or subfertility. The area under the curve, 0.85 (95% CI 0.74-0.96) indicates high test accuracy.
CA 125≥30u/ml is highly predictive of endometriosis in women with symptoms of pain and/or subfertility. CA 125 should be considered as a rule-in test for expediting the diagnosis and management of endometriosis, CA 125 <30u/ml is, however, unable to rule out endometriosis.
Z Evid Fortbild Qual Gesundhwes. 2016 Dec;118-119:24-30.
Economic burden of deep infiltrating endometriosis of the bowel and the bladder in Germany: The statutory health insurance perspective.
Until now, there has been little discussion of the costs of the deep infiltrating endometriosis (DIE) of the bowel or the bladder. The aim of the present secondary data analysis was to describe the population affected by this disease and to determine the economic burden in Germany from a payer’s perspective.
Health claims data of women diagnosed with DIE of the bladder or bowel, who were surgically treated as inpatients between Jan 1, 2008 and Dec 31, 2012, were evaluated retrospectively. All data were extrapolated on a national statutory health insurance (SHI) level and normalized based on the year of surgery (index year). Case-individual information on age, comorbidities and prescribed drugs were presented for the index year. Direct medical cost data were analysed before and after the index year, differentiated by cost sector and age group.
The data of 825 women with DIE were analysed. Sample size for different time points varied depending on insurance eligibility and continuous case information. The average age at surgery was 39 years. Besides DIE, 41 % of the women had at least one additional disease of the peritoneum. The mean annual total healthcare costs per DIE case were 12,868 Euros in the index year. Before surgery, mean annual costs varied between 548 and 2,475 Euros per case and after surgery between 1,739 and 2,818 Euros per case. In total, mean costs were higher in younger women as compared to older women, with a cost difference of 616 Euros over all time points.
Direct costs are highest during the year of surgical treatment, but DIE of the bowel and bladder places a substantial burden on the SHI also before and after surgery. Further studies on indirect costs would be desirable to complete the knowledge on the economic burden of DIE.
Urol Int. 2017;98(3):343-349.
Laparoscopic Extravesical Submucosal Tunneling Ureteroneocystostomy Combined with Psoas Hitch for Medium-Length Distal Ureteral Defects in Adults.
This study aims to describe the technique and feasibility of laparoscopic submucosal tunneling ureteroneocystostomy in combination with psoas hitch to restore urinary tract continuity in patients showing medium-length distal ureteral defects.
MATERIALS AND METHODS:
From January 2012 to April 2016, a total of 13 patients (4 males and 9 females) with a mean age of 37 years were performed with the laparoscopic operation of ureteral submucosal tunneling reimplantation combined with psoas hitch. The mean defective length was 5.5 cm (range 4-8 cm). The etiologies included ureteral strictures secondary to endoscopic laser lithotripsy in 2 patients, previous gynecological surgeries in 4, infiltrative ureteral endometriosis in 3, as well as ureteral strictures without obvious causes in the remaining 4.
The operations were successfully performed in all patients. The mean operating time was 179 min (range 150-230 min). The mean estimated blood loss was 32 mL (range 15-80 mL). The mean drainage time was 5.8 days (range 4-8 days). No major complications occurred during the perioperative period. The mean follow-up time was 25 months. All patients experienced symptomatic relief and showed good urine drainage.
Extravesical submucosal tunneling ureteroneocystostomy combined with psoas hitch under laparoscopy is a feasible and effective option for medium-length distal ureteral defects in selected patients.
Eur J Pharm Sci. 2017 Jan 1;96:542-550.
Evaluation of PLGA containing anti-CTLA4 inhibited endometriosisprogression by regulating CD4+CD25+Treg cells in peritoneal fluid of mouse endometriosis model.
Our study investigated poly(lactic-co-glycolic acid) (PLGA) as protein delivery vehicles encapsulate CTLA-4-antibody (anti-CTLA-4) which is essential for CD4+CD25+Treg cells suppressive function exposing superior potential for inhibiting endometriosis progress in mouse model than single anti-CTLA-4. Anti-CTLA-4 loaded PLGA combined to ligands CTLA-4 in surface of CD4+CD25+Treg cells which distributed in peritoneal fluid of mouse endometriosis model. The particle size, zeta potential of the anti-CTLA-4 loaded nanoparticles was detected by dynamic light scattering. Morphology of nanoparticles was evaluated by transmission electron microscopy (TEM). Confocal laser scanning microscopy (CLSM) indicated distribution of anti-CTLA-4 with PLGA or without in peritoneal fluid. Cumulative anti-CTLA-4 release from nanoparticles was evaluated by Micro BCA assay. The percentage of CD4+CD25+Treg cells in peritoneal fluid was demonstrated by flow cytometer. In vitro experiment we co-culture ectopic endometrial cells (EEC) with isolated CD4+CD25+Treg cells in peritoneal fluid (PF), proliferation and invasion of ectopic endometrial cells (EEC) was measured by BrdU ELISA assay and Matrigel invasion assay. In comparison with anti-CTLA-4 without nanoparticles, the bioconjugates PLGA/anti-CTLA-4 were tolerated in peritoneal fluid with a controlled release of anti-CTLA-4 in 3, 7, 14days. Moreover, PLGA/anti-CTLA-4 had superior protective regulation ability to reduce level of CD4+CD25+Treg cells in peritoneal fluid. Most strikingly, in vitro experiment, PLGA/anti-CTLA-4 exhibited better ability in inhibiting proliferation and invasion of ectopic endometrial cells in co-culture system compared with anti-CTLA-4. Progressively, PLGA/anti-CTLA-4 had better suppressive activity to inhibited IL-10 and TGF-beta secreted by CD4+CD25+Treg cells which indicating that PLGA/anti-CTLA-4 suppressed cells proliferation and invasion through reduced IL-10 and TGF-beta production. Thus, PLGA/anti-CTLA-4 may be a potential strategy for endometriosis therapy.
Hum Reprod. 2017 Feb;32(2):325-331
Total circulating microparticle levels are increased in patients with deep infiltrating endometriosis.
Are the levels of total circulating cell-derived microparticles (cMPs) and circulating tissue factor-containing microparticles (cMP-TF) increased in patients with endometriosis?
The levels of total cMP, but not cMP-TF, were higher in patients with endometriosis, and these were attributed to higher levels in patients with deep infiltrating endometriosis (DIE).
WHAT IS KNOWN ALREADY:
Previous studies have reported elevated levels of total cMP in inflammatory conditions as well as higher levels of other inflammatory biomarkers in endometriosis. Increased expression of tissue factor (a transmembrane receptor for Factor VII/VIIa) in eutopic and ectopic endometrium from patients with endometriosis has been described. There is no previous data regarding total cMP and cMP-TF levels in patients with endometriosis.
STUDY DESIGN, SIZE, DURATION:
A prospective case-control study including two groups of patients was carried out. The E group included 65 patients with surgically confirmed endometriosis (37 with DIE lesions) and the C group comprises 33 women without surgical findings of any form of endometriosis. Patients and controls were recruited during the same 10-month period. Controls were the next patient without endometriosis undergoing surgery, after including two patients with endometriosis.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Venous blood samples for total cMP and cMP-TF determinations were obtained at the time of surgery, before anesthesia at a tertiary care center. To assess total cMP, an ELISA functional assay was used and cMP-TF activity in plasma was measured using an ELISA kit.
MAIN RESULTS AND THE ROLE OF CHANCE:
Total cMP levels in plasma were higher in the E group compared with the C group (P < 0.0001). The subanalysis of endometriosis patients with DIE or with ovarian endometriomas without DIE showed that total cMP levels were higher in the DIE group (P = 0.001). There were no statistically significant differences in cMP-TF levels among the groups analyzed.
LIMITATIONS, REASONS FOR CAUTION:
This is a preliminary study in which the sample size was arbitrarily decided, albeit in keeping with previous studies analyzing cMP in other inflammatory diseases and other biomarkers in endometriosis. The control group included patients with other pathologies as well as healthy controls, and blood samples were taken at different phases of the cycle.
WIDER IMPLICATIONS OF THE FINDINGS:
Elevated total cMP levels in DIE patients may reflect an inflammatory and/or procoagulant systemic status in these patients. Further studies are warranted to confirm our findings and to assess the role of cMP levels in the pathophysiology of DIE.
STUDY FUNDING/COMPETING INTERESTS:
This study was supported in part by a grant from FIS-PI11/01560 and FIS-PI11/00977 within the ‘Plan Nacional de I + D + I’ and co-funded by the ‘ISCIII-Subdirección General de Evaluación’ and ‘Fondo Europeo de Desarrollo Regional (FEDER)’ and by the grant ‘Premi Fi de Residència Emili Letang 2015’ from the Hospital Clínic of Barcelona. The authors have no competing interests to disclose.
Oncotarget. 2017 Jan 24;8(4):5843-5852
Improved clinical outcomes of patients with ovarian carcinoma arising in endometriosis.
Despite enormous efforts to dissect the role of endometriosis in ovarian cancer development, the difference in prognosis between ovarian cancer patients with or without endometriosis remains elusive. The purpose of this study is to assess the association between endometriosis and the prognosis in patients with ovarian cancer.
Ovarian cancer arising in endometriosis tended to be presented as clear cell histology, early stage, less intraperitoneal metastasis and ascites, and lower CA125 level compared with those without endometriosis. Multivariate Cox regression analysis identified endometriosis as an independent prognostic factor for progression free survival (P = 0.002) and overall survival (P = 0.009) in all patients and especially for early stage. A nomogram integrating endometriosis, FIGO stage and CA125 was established to predict progression free survival and overall survival.
MATERIALS AND METHODS:
This study retrospectively enrolled 196 ovarian cancers arising or not in endometriosis judged by adjunctive use of CD10 immunohistochemistry in conjunction with H&E staining specimens. Clinicopathologic variables, progression-free survival (PFS) and overall survival (OS) were recorded. Kaplan-Meier analysis was performed to compare survival curves. Cox regression models were used to analyze the effect of endometriosis on PFS and OS. A prognostic nomogram was constructed based on the independent prognostic factors identified by multivariate analysis.
Endometriosis is an independent predictor of prognosis in ovarian cancer patients.
Semin Reprod Med. 2017 Jan;35(1):98-101.
Extrapelvic endometriosis is a rare and complex phenomenon. The pathologic mechanism of intrapelvic endometriosis is generally accepted as being largely due to retrograde menstruation through the fallopian tubes; however, the mechanism by which extrapelvic endometriosis forms has proven to be much more elusive. This article reviews the pathophysiology, clinical signs and symptoms, diagnostic techniques, and treatment recommendations for extrapelvic endometriosis of the umbilicus, abdominal wall, thorax, and vulva.
Semin Reprod Med. 2017 Jan;35(1):102-109.
Endometriosis in the Adolescent Patient.
The recognition and management of endometriosis in the adolescent patient is challenging. A strong clinical suspicion for endometriosis should be maintained in the adolescent who suffers from acyclic pelvic pain as well as absenteeism from school and lack of participation in daily activities. Risk factors include the presence of an obstructive Mullerian anomaly, a family history of endometriosis, and conditions that prolong exposure to endogenous and exogenous estrogens. Empiric medical therapy with nonsteroidal anti-inflammatory drugs and combined oral contraceptive pills may be considered in most adolescents with endometriosis. Failure of empiric therapy may warrant diagnostic laparoscopy, which affords a concomitant opportunity for treatment via excision of endometriosis. Endometriotic implants in the adolescent tend to be more atypical, appearing red/flame-like, clear/polypoid, or vesicular. Endometriosis tends to recur more often in adolescents when compared with adults, and the role of postoperative medical therapy for the suppression of disease progression is not entirely clear. Current knowledge on the impact of adolescent endometriosis on future fertility is limited but overall reassuring.
ACS Med Chem Lett. 2016 Sep 15;7(12):1028-1033.
Development of N-(4-Phenoxyphenyl)benzenesulfonamide Derivatives as Novel Nonsteroidal Progesterone Receptor Antagonists.
We report here development of N-(4-phenoxyphenyl)benzenesulfonamide derivatives as a novel class of nonsteroidal progesterone receptor (PR) antagonists. PR plays key roles in various physiological systems, including the female reproductive system, and PR antagonists are candidates for clinical treatment of multiple diseases, including uterine leiomyoma, endometriosis, breast cancer, and some psychiatric disorders. We found that the benzenesulfonanilide skeleton functions as a novel scaffold for PR antagonists, and we adopted 3-chlorobenzenesulfonyl derivative 20a as a lead compound for structural development. Among the synthesized compounds, 3-trifluoromethyl derivative 32 exhibited the most potent PR-antagonistic activity, with high binding affinity for PR and selectivity over androgen receptor (AR). It is structurally distinct from other nonsteroidal PR antagonists, including cyanopyrrole derivatives, and further modification is expected to afford novel selective PR modulators.
Mol Cell Biochem. 2017 Mar;427(1-2):81-89.
Is cytochrome P450 3A4 regulated by menstrual cycle hormones in control endometrium and endometriosis?
The estrogen-metabolizing activities of cytochrome P450 (CYP) enzymes have been implicated in endometriosis. However, their regulation in various sources of endometrial tissue under different hormonal conditions has not been clarified. Our objective was to study the hormone regulation of a specific CYP enzyme, namely CYP3A4, in control (n = 15) and endometriosis patients (n = 42). To this end, we evaluated mRNA expression (using real-time PCR) of CYP3A4 in tissue samples classified according to the phase of menstrual cycle at which they were obtained as confirmed by the related circulating hormone levels. Protein expression was also evaluated by Western Blot. In order to further investigate the hormonal regulation of CYP3A4, stromal cells from ovarian endometriotic lesions were cultured with the prevailing hormones of the distinct phases of the menstrual cycle. We observed that all control and endometriosis tissues express CYP3A4. Nevertheless, changes in CYP3A4 gene expression related to cycle phase were only seen in the control eutopic endometrium and not in samples from endometriosis patients, with an increase in the luteal phase. Stromal cells isolated from ovarian endometriotic lesions expressed CYP3A4 and their exposure to luteal phase-mimicking hormones (estradiol + progesterone) reduced CYP3A4 mRNA in parallel with a diminished expression of the corresponding receptors, estrogen receptor alpha and progesterone receptor. Our findings suggest that steroid hormones are able to regulate CYP3A4 mRNA expression, although the circulating levels of these hormones can only regulate control endometrium and not endometriosis tissues, probably because of dysregulated local steroid concentration in these latter samples.
Acta Obstet Gynecol Scand. 2017 Jun;96(6):659-667.
Endometriosis-associated infertility: aspects of pathophysiological mechanisms and treatment options.
Endometriosis is a common condition in women of reproductive age. In addition to pain, endometriosis may also reduce fertility. The causes of infertility in women with endometriosis may range from anatomical distortions due to adhesions and fibrosis to endocrine abnormalities and immunological disturbances. In some cases, the various pathophysiological disturbances seem to interact through mechanisms so far not fully understood. Whether surgery should be offered as a treatment option in endometriosis-associated infertility has become controversial, partly due to its modest or undocumented effect. Medical or hormonal treatment alone has little or no effect and should only be used in conjunction with assisted reproductive technology (ART). Of the various methods of ART, intrauterine insemination, due to its simplicity, can be recommended in women with minimal or mild peritoneal endometriosis, even though insemination may yield a lower success rate than in women without endometriosis. In vitro fertilization (IVF) is an effective treatment option in less-advanced disease stages, and the success rates are similar to the results in other causes of infertility. However, women with more advanced stages of endometriosishave lower success rates with IVF.
Nan Fang Yi Ke Da Xue Xue Bao. 2016 Dec 20;36(12):1626-1631.
Expression of ATPase inhibitory factor 1 in normal and pathological tissues of female reproductive system.
To determine ATPase inhibitory factor 1 (IF1) expression in normal and pathological tissue of female reproductive system to better understand the physiological role of IF1 in malignancies of the female reproductive system.
Surgical specimens of normal tissues and primary malignant tumors were obtained during the past 2 years, including 38 normal endometrium tissues, 33 endometriosis tissues, 30 endometrial adenocarcinoma tissues, 24 uterine myoideum tissues, 30 uterine fibroid tissues, 18 normal cervical tissues, 30 cervical squamous carcinoma tissues, 11 fallopian tube tissues, 19 fallopian tube adenocarcinoma tissues, 15 ovarian tissues, 21 ovarian endometrial adenocarinoma tissues, 30 decidua tissues, and 30 villus tissues. The expressions of IF1 protein and mRNA were assessed by immunohistochemistry, Western blotting and RT-PCR.
The expressions of IF1 were significantly increased in endometrial adenocarcinoma (P<0.01), cervical squamous carcinoma (P<0.01), fallopian tube adenocarcinoma (P<0.01) and ovarian endometrial adenocarinoma (P<0.01) as compared with those in normal tissues. In normal endometrium, IF1 expression was significantly reduced in the secretory phase as compared with the proliferation phase (P<0.01). In patients with endometriosis, IF1 protein expression increased obviously in endometriotic tissues as compared with eutopic and normal endometrial, but the expression IF1 mRNA was similar among the 3 tissues.
IF1 expression, increases abnormally in malignant tumors of the female reproductive system and may serve as a marker for malignancies of the female reproductive system as well as a promising pharmacological target for cancer treatment.
Case Rep Surg. 2016;2016:4312753.
Rectus Abdominis Endometrioma after Caesarean Section.
Isolated rectus abdominis muscle endometriosis is very uncommon with less than 20 case reports being published to date since its first description in 1984 by Amato and Levitt. We report another case of isolated rectus abdominis endometriosis in a 37-year-old patient with a previous caesarian section. We also discuss the diagnostic and treatment particularities in these patients. In our case, the treatment was only surgical and currently the patient is disease-free during the 24-month follow-up.