J Obstet Gynaecol Res. 2010 Feb;36(1):1-10. Mysteries of endometriosis pain: Chien-Tien Hsu Memorial Lecture 2009. Fraser IS. Department of Obstetrics and Gynaecology, University of Sydney, Sydney, New South Wales, Australia. The more that one looks at the condition endometriosis, the more one realises that it is a unique and complex condition exhibiting a bizarre range of deviations from normal endometrial and myometrial physiology, ...
Indian J Tuberc. 2017 Jul;64(3):173-177.
Concomitant female genital tuberculosis and endometriosis.
To demonstrate an association between female genital tuberculosis (FGTB) and endometriosis.
A total of 16 women who underwent laparoscopy (12 cases) or laparotomy (4 cases) and were found to have female genital tuberculosis and endometriosis were enrolled in this retrospective study.
The mean age and parity were 28.2 years and 0.2, respectively. Past history of tuberculosis was present in 75% of the women (pulmonary in 50%). Menstrual dysfunction (especially oligomenorrhoea and dysmenorrhoea), constitutional symptoms, infertility, abdominal pain and lump were the main complaints. Diagnosis of FGTB was made by positive acid-fast bacilli (AFB) on microscopy, culture of endometrial aspirate, positive polymerase chain reaction (PCR), histopathological finding of epitheliod granuloma or findings of TB on laparoscopy or laparotomy. Diagnosis of endometriosis was made by laparoscopy or laparotomy. Pelvic adhesions were seen in all women, whereas frozen pelvis was seen in 7 (43.7%) women. Surgery was performed, which was laparoscopic adhesiolysis in 12 (75%), drainage of endometrioma in 12 (75%), cystectomy in 8 (50%), and total abdominal hysterectomy with bilateral salpingo-oophorectomy in 4 (25%) cases. With more then one type of (surgery in many cases).
Female genital tuberculosis and endometriosis may have similar manifestations and can co-exist.
BMJ Case Rep. 2017 Jul 14;2017.
Laparoscopic excision of an inflammatory myofibroblastic tumour of the bladder disguised as deep infiltrating endometriosis.
Inflammatory myofibroblastic tumour (IMT) of the bladder is a rare tumour of indeterminate malignant potential with myofibroblastic differentiation, with a generally benign but rarely aggressive behaviour. Vesical IMT is usually treated by transurethral resection or partial cystectomy. Herein we describe a case of a woman who underwent laparoscopic excision of an IMT of the bladder, initially diagnosed as deep infiltrating endometriosis.
Mol Med Rep. 2017 Sep;16(3):3339-3344.
Protective effects of marrubiin improve endometriosis through suppression of the expression of RANTES.
Marrubiin can improve blood and lymph microcirculation disturbance, and has pharmacological effects in myocardial protection, anti‑inflammation and anti‑oxidation. The aim of the present study was to evaluate the protective effects of marrubiin on endometriosis through suppression of the expression of regulated on activation, normal T cell expressed and secreted (RANTES). Endometriotic cells were implanted into the peritoneal cavity of mice, and these mice were injected estradiol benzoate (30 µg/kg) once each day for 14 days. The mice with endometriosis were then treated with 12, 25 or 50 mg/kg marrubiin. Reverse transcription‑quantitative polymerase chain reaction was used to assess the mRNA expression of RANTES, and western blot analysis was used to analyze the protein expression of RANTES, TNF‑α and PGE2. Inflammation factors were measured by ELISA. Treatment with marrubiin effectively improved lesion regression and inhibited toxicity in the mouse model of endometriosis. Marrubiin significantly inhibited endometrial lesions and monocyte chemotaxis in the mice with endometriosis, and reduced U937 cell migration. Calcium mobilization, levels of tumor necrosis factor‑α and the secretion of RANTES were effectively suppressed by marrubiin treatment. The calcium levels were effectively induced, whereas the protein expression of prostaglandin E2 (PGE2) and formation of thromboxane B2 (TXB2) were effectively inhibited by marrubiin treatment. These findings indicated that the protective effect of marrubiin improved endometriosis in the mice through the suppression of inflammation and downregulation of the expression of RANTES, followed by mediation of the levels of calcium, PGE2 and TXB2.
Reprod Biol Endocrinol. 2017 Jul 17;15(1):52.
Differentiating mouse embryonic stem cells express markers of human endometrium.
Modeling early endometrial differentiation is a crucial step towards understanding the divergent pathways between normal and ectopic endometrial development as seen in endometriosis.
To investigate these pathways, mouse embryonic stem cells (mESCs) and embryoid bodies (EBs) were differentiated in standard EB medium (EBM). Immunofluorescence (IF) staining and reverse-transcription polymerase chain reaction (RT-PCR) were used to detect expression of human endometrial cell markers on differentiating cells, which were sorted into distinct populations using fluorescence-activated cell sorting (FACS).
A subpopulation (50%) of early differentiating mESCs expressed both glandular (CD9) and stromal (CD13) markers of human endometrium, suggestive of a novel endometrial precursor cell population. We further isolated a small population of endometrial mesenchymal stem cells, CD45-/CD146+/PDGFR-β+, from differentiating EBs, representing 0.7% of total cells. Finally, quantitative PCR demonstrated significantly amplified expression of transcription factors Hoxa10 and Foxa2 in CD13+ EBs isolated by FACS (p = 0.03).
These findings demonstrate that mESCs have the capacity to express human endometrial cell markers and demonstrate potential differentiation pathways of endometrial precursor and mesenchymal stem cells, providing an in vitro system to model early endometrial tissue development. This model represents a key step in elucidating the mechanisms of ectopic endometrial tissue growth. Such a system could enable the development of strategies to prevent endometriosis and identify approaches for non-invasive monitoring of disease progression.
J Ovarian Res. 2017 Jul 17;10(1):45.
Predictive factors of ovarian carcinoma for women with ovarian endometrioma aged 45 years and older in China.
To explore the risk factors of endometriosis-associated ovarian cancer (EAOC) in women with ovarian endometriosis (OEM) aged 45 years and above in China.
This study reviewed the medical records of 1038 women in total who were aged 45 years and above, surgical-pathologically diagnosed with ovarian endometriosis, and were treated at Peking Union Medical College Hospital between December 1996 and December 2016. Histology evaluation was used to determine whether the ovarian endometriosis specimen was with (n = 30) or without (n = 1008) ovarian cancer.
2.9% (30/1038) of women with the surgical-pathological diagnosis of ovarian endometriosis were found to have EAOC. Those patients with EAOC were prone to be in the postmenopausal status at the time of the diagnosis (OR 5.50, 95%CI 2.54-11.90, P < .001) and larger size of tumor (≥8 cm, OR 7.19, 95% CI 3.34-15.50, P < .001), and higher prevalence of coexisting with endometrial disorders (OR 4.11, 95%CI 1.73-9.73, P = .003). This study showed that patients of an older age when diagnosed with OEM, were at a higher risk of developing EAOC, respectively measuring of 1.7% (13/751) at 45-49 years, 5.6% (12/215) at 50-54 years, and 10.0%(5/50) at 55-59 years (P < 0.001).
This study showed that for women aged 45 years and above who were diagnosed with OEM, the independent risk factors of EAOC were menopausal status, tumor size of 8 cm or greater in diameter, and coexisting endometrial disorders. Therefore, intensive follow-ups or active interventions should be considered for them.
J Obstet Gynaecol Res. 2017 Jul;43(7):1093-1100.
New knowledge and insights about the malignant transformation of endometriosis.
Endometriosis may be a definitive risk factor for ovarian cancer, the most fatal gynecological cancer. The ability of endometriosis to transform into malignancy, first described by Dr. Sampson in 1925, is considered a rare occurrence, affecting approximately 1% of ovarian endometriomas. Recently we conducted a retrospective study regarding the malignant transformation of endometriosis in Japanese women. Many studies have reported a consistent correlation between endometriosis and ovarian cancer according to histological subtypes. However, the existing epidemiological evidence linking this association is insufficient to define the role of endometriosis as a cause of ovarian cancer and to influence changes to current clinical practice. Prospective cohort studies are therefore needed to clarify this issue. Additionally, the results of many molecular studies are conflicting, and earlier studies showing the molecular aberrations involved in genomic instability and mutation that enable malignant transformation have not been replicated in later studies. Careful long-term observation of a patient with endometrioma is required to detect possible subsequent incidence of malignant transformation. More importantly, a precise strategy should be set up for better prevention, early detection, specific diagnosis and treatment targeting molecular pathogenesis to understand the mechanisms of endometriosis-associated ovarian cancer. Clinicians need to be aware of the increased ovarian cancer risk in women with endometriosis.
Reprod Sci. 2017 Jan 1:
Histological and Immunohistochemical Characterization of the Similarity and Difference Between Ovarian Endometriomas and Deep Infiltrating Endometriosis.
Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) have long been recognized to have different histology and, as such, postulated to be 2 separate disease entities. Few studies, however, have attempted to elucidate the causes for their differences. Making use of ectopic endometrial tissue samples from 25 and 20 women with OMA and DIE, respectively, and control endometrial tissue samples from 25 women without endometriosis, we conducted an immunohistochemical analysis to evaluate the expression of a group of carefully chosen markers for epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), smooth muscle metaplasia (SMM), fibrosis, vascularity, hormonal receptors, and proteins involved in epigenetic modifications. We found that both OMA and DIE lesions exhibited the same cellular changes consistent with EMT, FMT, SMM, and fibrosis as already shown in animal models. Compared to OMA, DIE lesions underwent more thorough and extensive EMT, FMT, and SMM and, consequently, displayed significantly higher fibrotic content but less vascularity. The 2 conditions also showed different expression levels of hormonal receptors. Both OMA and DIE lesions, especially the latter, showed significantly higher staining of enhancer of zeste homolog 2, H3K9me3, and H3K27me3 than that of control endometrium, suggesting progressive epigenetic changes concomitant with cellular ones. Finally, proteins that are known to be involved in fibrogenesis, such as thymocyte differentiation antigen 1 and peroxisome proliferator-activated receptor γ , were also aberrantly expressed under both conditions. The many similarities shared by both OMA and DIE indicate that the 2 conditions may actually share the same pathogenesis/pathophysiology. Their differences, however, suggest that the source of these differences may result from the different lesional microenvironments.
Rev Med Suisse. 2017 Mar 15;13(554):612-616.
When sex hurts the couple : the case of endometriosis.
Sexual health is a critical aspect of quality of life and is also influenced by medical conditions and health care interventions, particularly when gynaecological disorders are involved. Dyspareunia is a common symptom of endometriosis, a cause of personal distress and a main raison for seeking treatment. Endometriosis negatively affects different domains of sexual function and specific biopsychological variables (chronic pain, recurrence, infertility) may further worsen quality of sexual function and relationship. Consequences of endometriosistreatment on global sexual functioning have not been featured prominently in the available literature, assuming wrongly that sexual pain improvement was always translated into a recovered sexual health.
Reprod Biol Endocrinol. 2017 Jul 18;15(1):53.
Arcyriaflavin a, a cyclin D1-cyclin-dependent kinase4 inhibitor, induces apoptosis and inhibits proliferation of human endometriotic stromal cells: a potential therapeutic agent in endometriosis.
We previously showed that microRNA-503 (miR-503) transfection into endometriotic cyst stromal cells (ECSCs) induced cell cycle arrest at the G0/G1 phase by suppressing cyclin D1. This finding prompted us to evaluate the potential therapeutic effects of cyclin D1 inhibitors in endometriotic cells. This study aimed to determine whether arcyriaflavin A, a representative inhibitor of cyclin D1-cyclin-dependent kinase 4 (CDK4), is beneficial in the treatment of endometriosis.
ECSCs were isolated from the ovarian endometriotic tissues of 32 women. The effects of arcyriaflavin A on cell viability and proliferation, vascular endothelial growth factor A expression, apoptosis, and cell cycle progression were evaluated using a modified methylthiazoletetrazolium assay, enzyme-linked immunosorbent assay (ELISA), Caspase-Glo® 3/7 assay, and flow cytometry.
Arcyriaflavin A significantly inhibited cell viability, proliferation, and angiogenesis of ECSCs as assessed using the 5-bromo-2-deoxyuridine (BrdU) and methylthiazoletetrazolium bromide (MTT) assays, and vascular endothelial growth factor (VEGF) ELISA. Arcyriaflavin A induced apoptosis as shown in the Caspase-Glo® 3/7 assay and cell death detection ELISA whilethe cell cycle was arrested at the G0/G1 phase.
The findings indicate that cyclin D1-CDK4 inhibitors may be promising candidates for the treatment of endometriosis. This is the first study to demonstrate the potential usefulness of arcyriaflavin A as a therapeutic agent for endometriosis. Further studies of the effects of cyclin D1-CDK4 inhibitors on endometriosismay provide useful information on pathogenesis and treatment.
J Pathol. 2017 Oct;243(2):137-147.
The peritoneum: healing, immunity and diseases.
The peritoneum defines a confined microenvironment, which is stable under normal conditions, but is exposed to the damaging effect of infections, surgical injuries, and other neoplastic and non-neoplastic events. Its response to damage includes the recruitment, proliferation and activation of a variety of haematopoietic and stromal cells. In physiologic conditions, effective responses to injuries are organized, inflammatory triggers are eliminated, inflammation quickly abates, and the normal tissue architecture is restored. However, if inflammatory triggers are not cleared, fibrosis or scarring occur and impaired tissue function ultimately leads to organ failure. Autoimmune serositis is characterized by the persistence of self-antigens and a relapsing clinical pattern. Peritoneal carcinomatosis and endometriosis are characterized by the persistence of cancer cells or ectopic endometrial cells in the peritoneal cavity. Some of the molecular signals orchestrating the recruitment of inflammatory cells in the peritoneum have been identified in the last few years. Alternative activation of peritoneal macrophages was shown to guide angiogenesis and fibrosis, and could represent a novel target for molecular intervention. This review summarizes current knowledge of the alterations to the immune response in the peritoneal environment, highlighting the ambiguous role played by persistently activated reparative macrophages in the pathogenesis of common human diseases.
Sci Rep. 2017 Jul 19;7(1):5883.
A balancing act: RNA binding protein HuR/TTP axis in endometriosis patients.
Endometriosis, a major reproductive pathology affecting 8-10% of women is characterized by chronic inflammation and immune dysfunction. Human antigen R (HuR) and Tristetraprolin (TTP) are RNA binding proteins that competitively bind to cytokines involved in inflammation including: tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6) among others, and stabilize and destabilize them, respectively. The aim of this study was to examine RNA binding protein (RNABP) HuR/TTP axis in endometriosis patients compared to menstrual stage matched healthy fertile controls in hopes of better understanding their contribution to the pathogenesis of endometriosis. Additionally, using a targeted in vitro siRNA approach, we examined whether knock-down of TTP can play a functional role on other RNABPs that competitively bind to inflammatory targets of TTP in both endometriotic and endometrial epithelial cell lines. Our results suggest that RNABPs TTP and HuR are dysregulated in endometriotic lesions compared to matched eutopic patient samples as well endometrium from healthy controls. Silencing of TTP in endometriotic and endometrial epithelial cells revealed differential response to inflammatory cytokines and other RNABPs. Our results suggest potential involvement of HuR/TTP RNA binding protein axis in regulation of inflammation in endometriosis.
Front Oncol. 2017 Jul 5;7:145.
Epithelial-to-Mesenchymal Transition in the Female Reproductive Tract: From Normal Functioning to Disease Pathology.
Epithelial-to-mesenchymal transition (EMT) is a physiological process that is vital throughout the human lifespan. In addition to contributing to the development of various tissues within the growing embryo, EMT is also responsible for wound healing and tissue regeneration later in adulthood. In this review, we highlight the importance of EMT in the development and normal functioning of the female reproductive organs (the ovaries and the uterus) and describe how dysregulation of EMT can lead to pathological conditions, such as endometriosis, adenomyosis, and carcinogenesis. We also summarize the current literature relating to EMT in the context of ovarian and endometrial carcinomas, with a particular focus on how molecular mechanisms and the tumor microenvironment can govern cancer cell plasticity, therapy resistance, and metastasis.
Eur J Obstet Gynecol Reprod Biol. 2017 Sep;216:51-55.
Effect of dienogest on pain and ovarian endometrioma occurrence after laparoscopic resection of uterosacral ligaments with deep infiltrating endometriosis.
To evaluate the effect of dienogest (DNG) in preventing the occurrence of pain and endometriomas after laparoscopic resection of uterosacral ligaments (USLs) with deep infiltrating endometriosis (DIE).
This retrospective analysis included 126 patients who underwent laparoscopic resection of USLs with DIE followed by postoperative administration of DNG or no medication. Every 6 months postoperatively, patients answered questions and underwent ultrasound examination to identify pain and/or endometrioma.
There were three (5.0%) cases of endometrioma in 59 patients from the DNG group and 21 (31.3%) cases in 67 patients from the no medication group (P=0.0002). Pain returned to preoperative levels in eight (11.9%) cases in the no medication group. No recurrence of pain occurred in the DNG group (P=0.0061).
The administration of DNG after resection of USLs with DIE significantly reduces the occurrence rate of endometriosis-related pain and endometriomas.
Clin J Pain. 2017 Jul 20.
Pain Catastrophizing and Pain Health-related Quality-of-life in Endometriosis.
To determine if pain catastrophizing is independently associated with pain health-related quality-of-life in women with endometriosis, independent of potential confounders.
Analysis of cross-sectional baseline data from a prospective database at a tertiary referral center for endometriosis/pelvic pain. Referrals to the center were recruited between December 2013 to April 2015, with data collected from online patient questionnaires, physical examination, and review of medical records. The primary outcome was health-related quality-of-life as measured by the 11-item pain subscale of the Endometriosis Health Profile-30 questionnaire. The Pain Catastrophizing Scale was the independent variable of interest. Other independent variables (potential confounders) included other psychological measures, pain severity, comorbid pain conditions, and social-behavioral and demographic variables. Multivariable linear regression was used to control for these potential confounders and assess independent associations with the primary outcome.
236 women were included (87% consent rate). The mean age was 35.0±7.3 years, and 98 (42%) had Stage I-II endometriosis, 110 (47%) had Stage III-IV endometriosis, and 28 (11%) were of unknown stage after review of operative records. Regression analysis demonstrated that higher pain catastrophizing (P<0.001), more severe chronic pelvic pain (P<0.001), more severe dysmenorrhea (P<0.001), and abdominal wall pain (positive Carnett test) (P=0.033) were independently associated with worse pain health-related quality-of-life.
Higher pain catastrophizing was associated with a reduced pain health-related quality-of-life in women with endometriosis at a tertiary referral center, independent of pain severity and other potential confounders.
Reprod Biomed Online. 2017 Oct;35(4):379-386.
PTGS2 down-regulation in cumulus cells of infertile women with endometriosis.
A deleterious effect of endometriosis on oocyte quality has been proposed. Evidence suggests that cumulus cells could be used as indirect biomarkers of oocyte quality. The PTGS2 gene, which encodes cyclooxygenase 2 (COX-2), is deregulated in endometriotic lesions and plays a crucial role in the acquisition of oocyte competence. To date, research evaluating PTGS2 expression in cumulus cells of infertile patients with endometriosis has not been conducted. The aim this study was to compare the expression levels of PTGS2 in cumulus cells of infertile women, with and without endometriosis, undergoing ovarian stimulation for intracytoplasmic sperm injection (ICSI). Therefore, a case-control study compared PTGS2 gene expression in the cumulus cells of 38 infertile patients with endometriosis and 40 without, using real-time polymerase chain reaction. For the first time, decreased expression of PTGS2 was found in cumulus cells of infertile women with endometriosis compared with controls (7.2 ± 10.5 versus 12.4 ± 15.7), which might be related to reduced levels of COX-2 in the cumulus cells of women with the disease. Consequently, we hypothesize that lower transcript levels of PTGS2 in cumulus cells may be involved in the impairment of oocyte quality, suggesting a possible mechanism involved in disease-related infertility.
Am J Obstet Gynecol. 2017 Nov;217(5):564.e1-564.e8
Effect of remote cesarean delivery on complications during hysterectomy: a cohort study.
Cesarean delivery is performed frequently worldwide, and follow-up studies that report complications at subsequent surgery are warranted.
The aim of the study was to investigate the association between a previous abdominal delivery and complications during a subsequent hysterectomy and to estimate the fraction of complications that are driven by the presence of adhesions.
This was a longitudinal population-based register study of 25354 women who underwent a benign hysterectomy at 46 hospital units in Sweden 2000-2014.
Adhesions were found in 45% of the women with a history of cesarean delivery. Organ injury affected 2.2% of the women. The risk of organ injury (adjusted odds ratio, 1.74; 95% confidence interval, 1.41-2.15) and postoperative infection (adjusted odds ratio, 1.26; 95% confidence interval, 1.15-1.39) was increased with previous cesarean delivery, irrespective of whether adhesions were present or not. The direct effect on organ injury by a personal history of cesarean delivery was estimated to 73%, and only 27% was mediated by the presence of adhesions. Previous cesarean delivery was a predictor of bladder injury (adjusted odds ratio, 1.86; 95% confidence interval, 1.40-2.47) and bowel injury (adjusted odds ratio, 1.83; 95% confidence interval, 1.10-3.03), but not ureter injury. A personal history of other abdominal surgeries was associated with bowel injury (adjusted odds ratio, 2.27; 95% confidence interval, 1.37-3.78), and the presence of endometriosis increased the risk of ureter injury (adjusted odds ratio, 2.15; 95% confidence interval, 1.34-3.44).
Previous cesarean delivery is associated with an increased risk of complications during a subsequent hysterectomy, but the risk is only partly attributable to the presence of adhesions. Previous cesarean delivery and presence of endometriosis were major predisposing factors of organ injury at the time of the hysterectomy, whereas background and perioperative characteristics were of minor importance.
Expert Opin Pharmacother. 2017 Sep;18(13):1391-1397.
Efficacy of elagolix in the treatment of endometriosis.
Much research has gone into developing medications that can be used to alleviate endometriosis-associated symptoms. In addition to already established medications, a new GnRH antagonist, elagolix, is in development. The novelty of this drug compared to other GnRH antagonists, is its nonpeptide structure, allowing it to be administered orally. Areas covered: We analyzed several Phase I, II and III clinical trials that have evaluated the safety and efficacy of this new medication. Expert opinion: Since many medications have been put on the market and have gained popularity for the treatment of endometriosis-associated symptoms, the demonstration of equality or superiority of effect, tolerability, as well as patient compliance should be assessed when introducing a new drug. While elagolix may have an advantage over established GnRH agonists, in that it does not lead to a ‘flare-up’ effect, it too, takes a toll on bone mineral density. Nevertheless, studies have shown that this new oral GnRH antagonist is well tolerated, and the side effects have been described as ‘mild or moderate’. However, in order to examine whether elagolix can compete with or even surpass established gold-standard medical treatments in this field, further studies that directly compare elagolix to said treatments, might be necessary.
Evid Based Complement Alternat Med. 2017;2017:7501015.
Identifying Chinese Herbal Medicine Network for Endometriosis: Implications from a Population-Based Database in Taiwan.
Endometriosis is a common but bothersome gynecological disease, and Chinese herbal medicine (CHM) is used for treating endometriosis. The aim of this study is to explore CHM network and core treatments for endometriosis by analyzing nationwide CHM prescription database.
From 1998 to 2013, the CHM prescriptions made primarily for endometriosis among women diagnosed with endometriosis (ICD-9-CM code: 671) by gynecologists during their reproductive age were collected. CHM network analysis was then carried out by using association rule mining and social network analysis.
A total of 12,986 CHM prescriptions made for endometriosis were analyzed. There were 556 kinds of CHM ever used, and, in average, each prescription was composed of 6.2 CHMs. Gui-Zhi-Fu-Ling-Wan (GZFLW) was used most frequently, followed by Cyperus rotundus (28.1% and 18.8% of all prescriptions, resp.). Additionally, the combination of Cyperus rotundus with GZFLW (8.0%) was the most frequently used combination of two CHMs. CHM network showed that GZFLW was the core CHM for endometriosis and graphically demonstrated the extensive coverage of TCM syndromes and pathogenesis of endometriosis.
CHM network provides graphical demonstration and summary of commonly used CHMs for endometriosis, and further studies are warranted based on these findings.
J Pathol Transl Med. 2017 Jul;51(4):433-440.
A Rare Case of Intramural Müllerian Adenosarcoma Arising from Adenomyosis of the Uterus.
Müllerian adenosarcomas usually arise as polypoid masses in the endometrium of post-menopausal women. Occasionally, these tumors arise in the cervix, vagina, broad and round ligaments, ovaries and rarely in extragenital sites; these cases are generally associated with endometriosis. We experienced a rare case of extraendometrial, intramural adenosarcoma arising in a patient with adenomyosis. A 40-year-old woman presented with sudden-onset suprapubic pain. The imaging findings suggested leiomyoma with cystic degeneration in the uterine fundus. An ill-defined ovoid tumor with hemorrhagic degeneration, measuring 7.5 cm in diameter, was detected. The microscopic findings showed glandular cells without atypia and a sarcomatous component with pleomorphism and high mitotic rates. There was no evidence of endometrial origin. To recognize that adenosarcoma can, although rarely, arise from adenomyosis is important to avoid overstaging and inappropriate treatment.
Lakartidningen. 2017 Jul 19;114.
Lösa cystor i lilla bäckenet – oväntat operationsfynd vid buksmärta.
Loose peritoneal cysts – unexpected finding at laparoscopic surgery for suspected extrauterine pregnancy, a case report A 29 year old woman was admitted to inpatient care in the 7th week of pregnancy due to three previous episodes of abdominal pain. At admission a suspected pseudogestational sac and 2 × 3 centimetres of fluid in the cul-de-sac was noted at vaginal ultrasound examination. After two days she again developed pain and a laparoscopy was performed due to suspected extrauterine pregnancy. Instead, three clusters of thin-walled, clear cysts was found lying loose in the cul-de-sac. There were also signs of endometriosis. The abdominal pain resolved gradually. At follow-up after one week a missed abortion was diagnosed. The pathologic-anatomic diagnosis was benign peritoneal cysts. Loose cysts are a more rare form of peritoneal inclusion cysts. They are benign but the risk of reoccurrence is about 50%. Some previous case reports indicate that growth of peritoneal cysts can be stimulated by pregnancy. In this case it is however unlikely that the small, loose cysts caused the woman’s pain.
Cochrane Database Syst Rev. 2017 Jul 25;7
Progesterone receptor modulators for endometriosis.
Endometriosis is defined as the presence of endometrial tissue (glands and stroma) outside the uterine cavity. This condition is oestrogen-dependent and thus is seen primarily during the reproductive years. Owing to their antiproliferative effects in the endometrium, progesterone receptor modulators (PRMs) have been advocated for treatment of endometriosis.
To assess the effectiveness and safety of PRMs primarily in terms of pain relief as compared with other treatments or placebo or no treatment in women of reproductive age with endometriosis.
We searched the following electronic databases, trial registers, and websites: the Cochrane Gynaecology and Fertility Group (CGFG) Specialised Register of Controlled Trials, the Central Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, clinicaltrials.gov, and the World Health Organization (WHO) platform, from inception to 28 November 2016. We handsearched reference lists of articles retrieved by the search.
We included randomised controlled trials (RCTs) published in all languages that examined effects of PRMs for treatment of symptomatic endometriosis.
DATA COLLECTION AND ANALYSIS:
We used standard methodological procedures as expected by the Cochrane Collaboration. Primary outcomes included measures of pain and side effects.
We included 10 randomised controlled trials (RCTs) with 960 women. Two RCTs compared mifepristone versus placebo or versus a different dose of mifepristone, one RCT compared asoprisnil versus placebo, one compared ulipristal versus leuprolide acetate, and four compared gestrinone versus danazol, gonadotropin-releasing hormone (GnRH) analogues, or a different dose of gestrinone. The quality of evidence ranged from high to very low. The main limitations were serious risk of bias (associated with poor reporting of methods and high or unclear rates of attrition in most studies), very serious imprecision (associated with low event rates and wide confidence intervals), and indirectness (outcome assessed in a select subgroup of participants). Mifepristone versus placebo One study made this comparison and reported rates of painful symptoms among women who reported symptoms at baseline.At three months, the mifepristone group had lower rates of dysmenorrhoea (odds ratio (OR) 0.08, 95% confidence interval (CI) 0.04 to 0.17; one RCT, n =352; moderate-quality evidence), suggesting that if 40% of women taking placebo experience dysmenorrhoea, then between 3% and 10% of women taking mifepristone will do so. The mifepristone group also had lower rates of dyspareunia (OR 0.23, 95% CI 0.11 to 0.51; one RCT, n = 223; low-quality evidence). However, the mifepristone group had higher rates of side effects: Nearly 90% had amenorrhoea and 24% had hot flushes, although the placebo group reported only one event of each (1%) (high-quality evidence). Evidence was insufficient to show differences in rates of nausea, vomiting, or fatigue, if present. Mifepristone dose comparisons Two studies compared doses of mifepristone and found insufficient evidence to show differences between different doses in terms of effectiveness or safety, if present. However, subgroup analysis of comparisons between mifepristone and placebo suggest that the 2.5 mg dose may be less effective than 5 mg or 10 mg for treating dysmenorrhoea or dyspareunia. Gestrinone comparisons Ons study compared gestrinone with danazol, and another study compared gestrinone with leuprolin.Evidence was insufficient to show differences, if present, between gestrinone and danazol in rate of pain relief (those reporting no or mild pelvic pain) (OR 0.71, 95% CI 0.33 to 1.56; two RCTs, n = 230; very low-quality evidence), dysmenorrhoea (OR 0.72, 95% CI 0.39 to 1.33; two RCTs, n = 214; very low-quality evidence), or dyspareunia (OR 0.83, 95% CI 0.37 to 1.86; two RCTs, n = 222; very low-quality evidence). The gestrinone group had a higher rate of hirsutism (OR 2.63, 95% CI 1.60 to 4.32; two RCTs, n = 302; very low-quality evidence) and a lower rate of decreased breast size (OR 0.62, 95% CI 0.38 to 0.98; two RCTs, n = 302; low-quality evidence). Evidence was insufficient to show differences between groups, if present, in rate of hot flushes (OR 0.79, 95% CI 0.50 to 1.26; two RCTs, n = 302; very low-quality evidence) or acne (OR 1.45, 95% CI 0.90 to 2.33; two RCTs, n = 302; low-quality evidence).When researchers compared gestrinone versus leuprolin through measurements on the 1 to 3 verbal rating scale (lower score denotes benefit), the mean dysmenorrhoea score was higher in the gestrinone group (MD 0.35 points, 95% CI 0.12 to 0.58; one RCT, n = 55; low-quality evidence), but the mean dyspareunia score was lower in this group (MD 0.33 points, 95% CI 0.62 to 0.04; low-quality evidence). The gestrinone group had lower rates of amenorrhoea (OR 0.04, 95% CI 0.01 to 0.38; one RCT, n = 49; low-quality evidence) and hot flushes (OR 0.20, 95% CI 0.06 to 0.63; one study, n = 55; low quality evidence) but higher rates of spotting or bleeding (OR 22.92, 95% CI 2.64 to 198.66; one RCT, n = 49; low-quality evidence).Evidence was insufficient to show differences in effectiveness or safety between different doses of gestrinone, if present. Asoprisnil versus placebo One study (n = 130) made this comparison but did not report data suitable for analysis. Ulipristal versus leuprolide acetate One study (n = 38) made this comparison but did not report data suitable for analysis.
Among women with endometriosis, moderate-quality evidence shows that mifepristone relieves dysmenorrhoea, and low-quality evidence suggests that this agent relieves dyspareunia, although amenorrhoea and hot flushes are common side effects. Data on dosage were inconclusive, although they suggest that the 2.5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators.
Clin Obstet Gynecol. 2017 Sep;60(3):467-476.
A Review of the Epigenetic Contributions to Endometriosis.
Epigenetic influences have been postulated to affect the course of endometriosis. DNA methyltransferases, estrogen and progesterone receptors, micro-RNAs, and histone deacetylators, have shown differential expression in endometriosis compared with normal endometrium. Others such as aromatase, Steroid Factor-1, COX-2, and Homeobox A10 also have epigenetic modifications in endometriosis. Limitations in this area of research include heterogeneity in study design, patient populations, and methods of analysis. Larger, controlled studies are needed. Future targeted uses of this work may include using methylomes to noninvasively diagnose endometriosis, or targeting histone-deacetylase inhibitors for treatment.
Clin Obstet Gynecol. 2017 Sep;60(3):477-484.
Surgery and Endometriosis.
Care of the endometriosis patient today can be complex and difficult. Once medical management has been exhausted and symptoms persist patients desire further treatment options. This chapter takes an evidence-based approach at discussion of patient surgcical options for treatment of endometriosis symptoms. Surgical techniques, success rates, patient satisfaction, and risks must be discussed and understood at depth before planning patient surgical intervention. This chapter provides reference to current surgical management options and symptom relief following those interventions.
Clin Obstet Gynecol. 2017 Sep;60(3):497-502.
Fertility and Endometriosis.
Approximately 30% to 50% of women that have the diagnosis of endometriosis also struggle with infertility. Twenty five percent to 50% of women diagnosed with infertility also have endometriosis, but the endometriosismay not be severe enough to be the primary etiology of infertility. White women have been reported to be more likely than African American women to have endometriosis. In addition, risk factors for endometriosis include below average body mass index, smoking, and alcohol use. Below is a discussion regarding the various ways in which endometriosis decreases fecundity and also discusses potential outcomes of fertility treatments regarding endometriosis.
Clin Obstet Gynecol. 2017 Sep;60(3):503-516.
Endometriosis and Imaging.
Endometriosis is a condition with variable location, size, and lesion composition which poses a diagnostic imaging challenge for the practicing gynecologist. Transvaginal ultrasound and magnetic resonance imaging are the most frequent imaging techniques used for its evaluation, but transvaginal ultrasound should be the first-line approach, as it is often sufficient, followed by modified ultrasound techniques. Magnetic resonance imaging should be considered when a diagnosis has not been achieved by sonographic means or when the renal system needs to be concurrently evaluated. Computed tomography has no role in the routine evaluation of endometriosisexcept in very few particular scenarios.
Clin Obstet Gynecol. 2017 Sep;60(3):517-523.
Endometriosis and Fertility Preservation.
Endometriosis is common, affecting 5% to 10% of reproductive age women. Nearly half of women with surgical evidence of endometriosis fail to achieve spontaneous pregnancy. Surgical treatment of endometriosis can be detrimental to ovarian reserve. In the absence of surgical intervention, ovarian reserve may still be negatively impacted over time. Fertility preservation was developed for women requiring gonadotoxic treatments. Improved methods have led to greater consideration of offering these services to women with other disease processes that threaten ovarian reserve. This chapter will present the debate regarding use of fertility preservation in management of endometriosis, and outline the need for further studies.
Clin Obstet Gynecol. 2017 Sep;60(3):531-538.
Genetics of Endometriosis.
Endometriosis is a complex, puzzling disease in women of reproductive age. The exact cause of the disease is unknown; however, different genetic and environmental factors contribute to the evolution of the disorder. Further investigation has led to the discovery of inheritance as a complex genetic trait. Candidate genes were identified to isolate regions of genes that affect disease risk. Additional linkage studies have been performed to map specific genes along the entire genome. Recent advances to determine the genetic component of endometriosisinclude genome-wide association studies. This chapter focuses on different approaches to identify the genetic links of endometriosis and its pathogenesis.
Clin Obstet Gynecol. 2017 Sep;60(3):539-542.
Summary of Future Developments.
Endometriosis is a chronic disease with the potential to cause devastating clinical manifestations such as infertility and chronic pelvic disease. Current treatment is limited to surgical intervention and pharmacologic therapy targeting estrogen and progesterone to suppress ectopic endometrial tissue proliferation. Undesired side effects and contraindications to the use of hormonal medications may reduce treatment options. As the pathogenesis of endometriosis continues to be investigated, new therapies will emerge. The identification of genes involved in the development of endometriosis may allow targeted therapy to prevent or cure disease. In addition, increasing knowledge of the inflammatory pathways that promote ectopic endometrial growth will permit the development of pharmacologic agents to manipulate these signaling pathways. Utilization of selective progesterone receptor modulators, aromatase inhibitors, and modern gonadotropin-releasing hormone antagonists provide more options to manage disease when traditional treatment fails. Individualized therapeutic strategies will soon be a reality as a greater understanding of endometriosis is obtained through the investigation of genomic studies, molecular pathways, and environmental influences.
Khirurgiia (Mosk). 2017;(7):44-48.
The combination of endoscopic techniques in the diagnosis and treatment of various forms of infertility in women.
To improve the methods of simultaneous laparoscopy and hysteroscopy for the diagnosis and treatment of various forms of secondary infertility.
MATERIAL AND METHODS:
420 women with various forms of infertility were examined and treated at the Caspian Hospital (Institute of Obstetrics and Gynecology). Patients were divided into three groups: tubal-peritoneal infertility – 212 women, different forms of endometriosis – 113 patients, polycystic ovarian disease – 95 women. We proposed safer method of laparoscopic surgery.
There were no injuries of internal organs and bleeding from the puncture site if Veress needle and the first ‘blind’ trocar were deployed according to proposed method. We consider that choice of operative hysteroscopy technique should be differentiated in case of benign gynecological diseases. Anesthesia-free operative hysteroscopy by S. Bettocchi may be performed if diagnostic hysteroscopy is tolerable. Simultaneous laparoscopy and hysteroscopy are safe for patients.
J Bodyw Mov Ther. 2017 Jul;21(3):569-573.
The effectiveness of osteopathic manipulative treatment in an abnormal uterine bleeding related pain and health related quality of life (HR-QoL) – A case report.
Abnormal uterine bleeding is characterized by painful and/or excessive menorrhea, chronic pelvic pain due to the endometriosis (Em). Osteopathic treatment is commonly used in the gynecological dysfunctions. The aim of the present case study was to explore the effect of osteopathic treatment (OT) for a woman with abnormal uterine bleeding related pain and quality of life (QoL). We reported a case of 29 year old female who presented with chief complaints of increased flow during periods, lower abdominal pain, leukorrhoea, lower back pain and with occasional constipation for the last 3 years. Patient is a mother of 6 years old male child born with normal delivery. On diagnostic ultrasonography the uterus was found bulky with insignificant endometriosis and no other abnormality was detected. She did not have any relevant past medical and surgical history. The pre and post osteopathic treatment measurements were measured using Visual Analog Scale (VAS) and the health related quality of life (HR-QoL) questionnaire called short form Endometriosis Health Profile Questionnaire (EHP) – 5. In the present case the pain due to the endometriosis was treated with the osteopathic treatment consists of all the major diaphragms’ release (release of pelvic diaphragm, abdominal diaphragm, thoracic outlet release and hyoid diaphragm) during the first session and in the second session gastro-esophageal (GE) junction release, sigmoid colon release, cranial therapy to the occiput, sacral release and dural tube rocking. Following that improvement of pain from VAS 8.3/10 to 3.9/10 and QoL improvement from EHP-5, 72/100 to 26/100 was noted. Osteopathic manipulative approach (OMA) in the patient with Em might improve the abnormal uterine bleeding related pain and health related quality of life (HR-QoL).
Sci Rep. 2017 Jul 28;7(1):6765.
KRAS Activation and over-expression of SIRT1/BCL6 Contributes to the Pathogenesis of Endometriosis and Progesterone Resistance.
Endometriosis is an inflammatory condition that is associated with progesterone resistance and cell proliferation, resulting in pain, infertility and pregnancy loss. We previously demonstrated phosphorylation of STAT3 in eutopic endometrium of infertile women with this disorder leading to over-expression of the oncogene BCL6 and stabilization of hypoxia-induced factor 1 alpha (HIF-1α). Here we report coordinated activation of KRAS and over-expression of Sirtuin 1 (SIRT1), a histone deacetylase and gene silencer, in the eutopic endometrium from women with endometriosis throughout the menstrual cycle. The mice with conditional activation of KRAS in the PGR positive cells reveal an increase of SIRT1 expression in the endometrium compared to control mice. The expression of progesterone receptor target genes including the Indian Hedgehog pathway genes are significantly down-regulated in the mutant mice. SIRT1 co-localizes with BCL6 in the nuclei of affected individuals and both proteins bind to and suppress the promoter of GLI1, a critical mediator of progesterone action in the Indian Hedgehog pathway, by ChIP analysis. In eutopic endometrium, GLI1 expression is reduced in women with endometriosis. Together, these data suggest that KRAS, SIRT1 and BCL6 are coordinately over-expressed in eutopic endometrium of women with endometriosis and likely participate in the pathogenesis of endometriosis.
Sci Rep. 2017 Jul 28;7(1):6804.
Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis.
EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis is unclear. Here, we show that EZH2 expression, along with its associated PRC2 proteins, is significantly elevated in ectopic and eutopic endometrium from women with endometriosis as compared with control endometrium. EZH2 knockdown or inhibition restored the epithelial phenotypes of endometriotic epithelial cells, concomitant with the upregulation of E-cadherin and downregulation of vimentin and transcription factors (Snail and Slug) as well as reduced cellular migratory and invasive propensity. Conversely, overexpression of EZH2 induced the expression of Snail, Slug and vimentin and suppresses E-cadherin expression. In vivo administration of 3-Deazaneplanocin A (DZNep), an EZH2 inhibitor, significantly inhibited the growth of endometriotic lesions and improved generalized hyperalgesia, along with attenuated EMT and reduced fibrosis in endometriosis. Notably, platelets induced EZH2 upregulation and increased H3K27 and H3K9 trimethylation levels in endometriotic epithelial cells. These data identify EZH2 as a novel driver of EMT in endometriosis, implicates the link between wound healing and epigenetic changes in the context of endometriosis, and underscore the role of platelets in the development of endometriosis.
BJOG. 2017 Jul 29. doi: 10.1111/1471-0528.14838.
Diagnosis and management of endometriosis: a systematic review of international and national guidelines.
The development of robust clinical guidelines requires standardised development methods informed by robust evidence synthesis.
We evaluated the methodological quality of endometriosis guidelines, mapped their recommendations, and explored the relationships between recommendations and research evidence.
We searched:  EMBASE;  Medline; and  Pubmed from inception to February 2016.
We included guidelines related to the diagnosis and management of endometriosis.
DATA COLLECTION AND ANALYSIS:
The search strategy identified 879 titles and abstracts. We include two international and five national guidelines. Four independent authors assessed the methodological quality of included guidelines using the Appraisal of Guidelines for REsearch & Evaluation (AGREE-II) instrument and systematically extracted the guideline recommendations and supporting research evidence.
One hundred and fifty-two different recommendations were made. Ten recommendations (7%) were comparable across guidelines. The European Society of Human Reproduction and Embryology was objectively evaluated as the highest quality guideline (methodological quality score: 88/100). There was substantial variation between the supporting evidence presented by individual guidelines for comparable recommendations. Forty-two recommendations (28%) were not supported by research evidence. No guideline followed the standardised guideline development methods (AGREE-II).
There is substantial variation in the recommendations and methodological quality of endometriosis guidelines. Future guidelines should be developed with reference to high quality methods, in consultation with key stakeholders, including women with endometriosis, ensuring their scope can truly inform clinical practice and eliminate unwarranted and unjustified variations in clinical practice. This article is protected by copyright. All rights reserved.
Int J Gynaecol Obstet. 2017 Nov;139(2):149-154.
Risk of appendiceal endometriosis among women with deep-infiltrating endometriosis.
To determine whether deep-infiltrating endometriosis (DE) carries an increased risk of appendiceal endometriosis (AppE) as compared with superficial endometriosis or no endometriosis.
In a retrospective study, data were obtained by chart review of an internal database for women who underwent coincidental appendectomy during benign gynecologic surgery between July 2009 and February 2014 at a tertiary referral center in the USA. Univariate, bivariate, and regression analyses were performed. The primary exposure was surgically documented endometriosis (DE, superficial, or no endometriosis). The primary outcome was AppE.
Endometriosis was diagnosed for 151 (38.2%) of 395 women; 82 (54.3%) had DE. The prevalence of AppE was 13.2% (52/395) overall; 8 (11.6%) of 69 women with superficial endometriosis and 32 (39.0%) of 82 with DE were affected. Frequency of AppE was increased among women with DE, abnormal appendix appearance, and surgical indication (all P<0.001). Women with DE had a 5.9-fold (95% confidence interval [CI] 2.9-11.9) higher risk of AppE compared with women without endometriosis, controlling for appendiceal appearance and surgical indication, and a 2.7-fold (95% CI 1.2-6.2) higher risk of AppE compared with those with superficial endometriosis.
Women with DE have increased risk of AppE. Coincidental appendectomy should form part of complete endometriosis excision for these patients.
Ci Ji Yi Xue Za Zhi. 2017 Jan-Mar;29(1):55-58.
Clear cell carcinoma arising from scar endometriosis: A case report and literature review.
Scar endometriosis is uncommon and defined as the presence of ectopic endometrial glands in abdominal soft tissues after a gynecological operation. Malignant transformation has been reported but remains rare. Carcinogenesis occurs in ectopic endometrial tissue with repeated hormone stimulation during the menstrual cycle. We present a case of clear cell carcinoma directly arising from scar endometriosis after a cesarean section and review all 16 cases reported.
Int J Mol Sci. 2017 Jul 29;18(8).
Role of Plasminogen Activator Inhibitor Type 1 in Pathologies of Female Reproductive Diseases.
Normal pregnancy is a state of hypercoagulability with diminishing fibrinolytic activity, which is mainly caused by an increase of plasminogen activator inhibitor type 1 (PAI-1). PAI-1 is the main inhibitor of plasminogen activators, including tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA). In human placentas, PAI-1 is expressed in extravillous interstitial trophoblasts and vascular trophoblasts. During implantation and placentation, PAI-1 is responsible for inhibiting extra cellular matrix (ECM) degradation, thereby causing an inhibition of trophoblasts invasion. In the present study, we have reviewed the literature of various reproductive diseases where PAI-1 plays a role. PAI-1 levels are increased in patients with recurrent pregnancy losses (RPL), preeclampsia, intrauterine growth restriction (IUGR), gestational diabetes mellitus (GDM) in the previous pregnancy, endometriosis and polycystic ovary syndrome (PCOS). In general, an increased expression of PAI-1 in the blood is associated with an increased risk for infertility and a worse pregnancy outcome. GDM and PCOS are related to the genetic role of the 4G/5G polymorphism of PAI-1. This review provides an overview of the current knowledge of the role of PAI-1 in reproductive diseases. PAI-1 represents a promising monitoring biomarker for reproductive diseases and may be a treatment target in the near future.
Curr Med Res Opin. 2017 Dec;33(12):2229-2234
Surgical outcomes of laparoscopic endometriosis surgery: a 6-year experience.
The aim of the present study was to review 6-year experience on the surgical outcomes of laparoscopic endometriosis surgery.
A cohort study was performed in Shiraz University of Medical Sciences using data from medical records of 1315 cases of patients with endometriosis undergoing laparoscopic surgery with follow-up of 6 to 72 months.
This study concerned a cohort of 1315 patients diagnosed with endometriosis operated between April 2010 and April 2016, 1086 (82.5%) of whom were in stage III and IV, 968 (73.61%) had endometrioma (regardless of having DIE or peritoneal involvement), and 347 (26.39%) of patients had either DIE or peritoneal involvement without endometrioma. Regarding the patients, unilateral endometrioma was statistically significant in the left ovary (P = 0.002). One hundred and thirty-three (10.7%) rectal wall, 7 (0.32%) sigmoid colon, 4 (0.18%) vagina, 125 (5.6%) ureter, 33 (1.52) bladder involvements were detected. Prior to operation, the pain VAS score was 8.23 ± 2.03, which decreased to 4.46 ± 2.47 in 93.07% of patients. Fifty-three patients (6.56%) needed reoperation. Sixty-six (33.1%) of infertile women had spontaneous pregnancy and (25%, n = 15) became pregnant using IUI or ART post operatively.
Surgical treatment of endometriosis seems to be an effective treatment. DIE can be present in the absence of endometrioma. The rate of left endometrioma is higher due to pressure effect of sigmoid colon. Nonetheless, if an expert surgeon performs this procedure, not only the rate of postoperative complications, but also the possibility of recurrence diseases would decrease.
BMB Rep. 2017 Aug;50(8):429-434.
Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression.
Interestingly, transforming growth factor β1 (TGF-β1) expression was higher in endometriotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to mesothelial cells was also higher than that of normal endometrial cells. Moreover, TGF-β1 directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of αV, α6, β1, and β4 via the activation of the TGF-β1/TGF-βRI/Smad2 signaling pathway. Conversely, the adhesion of TGF-β1-stimulated endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific TGF-β1-mediated integrins αV, β1, and β4 on the endometrial cell membrane. Taken together, our results demonstrate that secreted TGF-β1 enhances the adhesion of endometrial cells to mesothelial cells by inducing the expression of integrin heterodimers αVβ1, α6β1, and α6β4 via the activation of the TGF-βRI/Smad2 signaling pathway, leading to endometriosis formation outside the uterus.
Stem Cells Int. 2017;2017:4794827.
Characteristics of Human Endometrium-Derived Mesenchymal Stem Cells and Their Tropism to Endometriosis.
Human endometrial tissue has become an attractive source of mesenchymal stem cells (MSCs) for cell-based therapies because these MSCs can be easily harvested and have tumour tropism as well as reduced immunogenic and inflammatory properties. Our study aimed to obtain and characterise human endometrial mesenchymal stem cells (EMSCs) and assess their endometriosis tropism. EMSCs were successfully isolated from the endometrium of women undergoing laparoscopy for idiopathic infertility. The EMSCs presented a fibroblast-like morphology during culture. Flow cytometry analyses showed that the cells were positive for the specific stem cell markers CD73, CD90, CD105, CD166, and HLA-ABC (major histocompatibility complex class I (MHC I)) but negative for CD14, CD34, CD45, and HLA-DR (MHC II). Reverse transcription polymerase chain reaction results showed that the EMSCs expressed the stem cell marker OCT4. The EMSCs could differentiate into osteocytes, adipocytes, and chondrocytes under certain conditions. The EMSCs had a high tropism to endometriosis without tumourigenicity. This study enhances the possibility of using EMSCs as drug carriers in human cell-based therapies. Meanwhile, future research could also focus on developing targeted therapies for endometriosis.
Wien Klin Wochenschr. 2017 Oct;129(19-20):717-726
Catamenial pneumothorax since introduction of video-assisted thoracoscopic surgery : A systematic review.
Catamenial pneumothorax is an uncommon form of spontaneous pneumothorax in women. The exact epidemiology and pathogenesis remain elusive. Video-assisted thoracoscopic surgery is used for diagnostic and therapeutic purposes.
The aim of this review was to analyze the demographic features, intraoperative findings, treatment methods and outcome in catamenial pneumothorax patients. In addition, we assessed the relationship between catamenial pneumothorax and pelvic endometriosis.
A PubMed search of medical literature, published from January 1993 (video-assisted thoracoscopic surgery first described in literature) to January 2015, using the keywords “catamenial pneumothorax” was performed. Our study complied with the preferred reporting of items for systematic reviews and meta-analysis principles. A total of 182 patients were included in the analysis, including 4 patients treated at our institution.
The inclusion criteria of were recurrent (at least two) episodes of spontaneous pneumothorax in relation to onset of menses.
DATA SELECTION AND ANALYSIS:
Age at time of diagnosis, side affected, diagnosis of pulmonary endometriosis, intraoperative findings, histological confirmation of thoracic endometriosis, methods of treatment and outcome were recorded.
In 2.9% of the patients no pathological lesions were found; however, 59.3% had endometrial implants and 57.0% diaphragmatic perforations. Pelvic endometriosis was reported in 39.5% patients. Patients with diagnosed pelvic endometriosis showed a significantly higher rate of endometrial implants and histologically confirmed endometriosis lesions than patients without pelvic endometriosis. In 26.9% of patients, recurrence was observed after treatment.
Video-assisted thoracoscopic surgery provides good diagnostic and therapeutic results; however, 25% of patients experienced recurrence despite adequate treatment. A strong association exists between thoracic and pelvic endometriosis in catamenial pneumothorax patients.
Case Rep Obstet Gynecol. 2017;2017:8243204.
A Case with Severe Endometriosis, Ovarian Hyperstimulation Syndrome, and Isolated Unilateral Pleural Effusion after IVF.
We present a very rare case of right-sided isolated pleural effusion in a patient with severe endometriosis who, in relation to in vitro fertilization (IVF), developed ovarian hyperstimulation syndrome (OHSS). Earlier laparotomy showed grade IV endometriosis including endometriotic implants of the diaphragm. The patient had no known risk factors for OHSS and only a moderate number of oocytes aspirated. She received, however, repeated hCG injections for luteal support. The patient did not achieve pregnancy but was hospitalized due to pain in the right side of the chest and dyspnoea. A chest computed tomography (CT) showed a pleural effusion on the right side. Total of 1000 ml of pleural fluid was drained after a single thoracentesis. After three days, the symptoms and fluid production ceased. Ascites is a common finding in OHSS, but pleural effusions are rare. Further, isolated pleural effusions have not previously been described in a patient with endometriosis. We suggest that the repeated hCG injections induced effusions from the endometriotic lesions at the diaphragm and as a consequence this patient developed isolated hydrothorax.
Environ Pollut. 2017 Oct;229:837-845.
Polychlorinated biphenyls and its potential role in endometriosis.
With the progress of global industrialization and environmental deterioration, the relationship between human health and the living environment has become an increasing focus of attention. Polychlorinated biphenyls (PCBs, including dioxin-like polychlorinated biphenyls and non-dioxin-like polychlorinated biphenyls), as part of the organic chlorine contaminants, have been suspected as playing a role in the etiopathogenesis of endometriosis. Several population-based studies have proposed that exposure to PCBs may increase the risk of developing endometriosis, while some epidemiological studies have failed to find any association between PCBs and endometriosis. The purpose of this review is to discuss the potential pathophysiological relationship between endometriosis and PCBs with a focus on both dioxin-like polychlorinated biphenyls and non-dioxin-like polychlorinated biphenyls.