Best Pract Res Clin Obstet Gynaecol. 2018 Feb 15.
From pathogenesis to clinical practice: Emerging medical treatments for endometriosis.
Endometriosis is a chronic disease, and a lifelong management plan should be developed by using pharmacological treatment and surgical procedures. The pathogenesis of endometriosis is complicated and has not been definitively established. The mechanisms involved are numerous, and their understanding is constantly evolving. Currently, the first-line drugs act by blocking ovarian function, creating an hypoestrogenic environment. The blockade of estrogen secretion and receptor activity and the activation of progesteron receptors are the main target of several current drugs, as well as those under development. The oral GnRH antogonists, the aromatase inhibitors, SERMs, and SPRMs are the hormonal drugs currently studied for treating endometriosis. The increasing knowledge of the pathogenesis has allowed the development of new treatments. The most studied are the anti-inflammatory drugs, starting from the new NSAIDs to the monoclonal antibodies and the statins. Among the antiangiogenic compounds, a role is suggested for Icon, PPARs, and HDACIs. A new class of drugs is the cannabinoids. The aim of this review was to investigate the new therapeutic hormonal and non-hormonal alternatives to standard treatments.
Hum Reprod. 2018 Mar 19.
Role of interleukin-32 in the pathogenesis of endometriosis: in vitro, human and transgenic mouse data.
Does interleukin-32 (IL-32) play a role in the pathogenesis of endometriosis?
IL-32 might be involved in the pathogenesis of endometriosis through increased viability, proliferation and invasion of endometrial cells.
WHAT IS KNOWN ALREADY:
Endometriosis is characterized as a chronic inflammatory disease and several proinflammatory cytokines are suggested to be involved in its pathogenesis and pathophysiology. IL-32, recognized as a new proinflammatory cytokine and a strong inducer of other proinflammatory cytokines, has been shown to serve as a key modulator in several chronic inflammatory diseases.
STUDY DESIGN, SIZE, DURATION:
This study included comparison of IL-32 levels in the peritoneal fluids between women with and without endometriosis, in-vitro experiments using Ishikawa cells and endometrial stromal cells (ESCs), and experiments on IL-32 transgenic mice and wild-type mice with induced endometriosis.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
IL-32 levels in the peritoneal fluids were measured using enzyme-linked immunosorbent assays. Cell viability, expression of proliferating cell nuclear antigen (PCNA), and cellular invasiveness were analyzed following in-vitro treatment of Ishikawa cells and ESCs with recombinant IL-32 alpha (α) and gamma (γ). Ectopic endometriotic lesions were compared between IL-32 transgenic mice and wild-type mice after autologous endometrial transplantation with immunohistochemistry for Ki-67 antigen and PCNA.
MAIN RESULTS AND THE ROLE OF CHANCE:
The peritoneal fluid concentration of IL-32 was significantly higher in patients with advanced stage endometriosis compared with the controls. In-vitro treatment with IL-32 α and γ caused significant increases in cellular viability, PCNA expression, and invasiveness in Ishikawa cells and ESCs. The IL-32 transgenic mice had a significantly larger size of the ectopic endometrial lesions with higher expression of Ki-67 antigen and PCNA compared with wild-type mice.
LARGE SCALE DATA:
LIMITATIONS, REASONS FOR CAUTION:
It is still unclear whether IL-32 is a main regulator, or one of several downstream proinflammatory cytokines, causing establishment and/or progression of endometriosis.
WIDER IMPLICATIONS OF THE FINDINGS:
Further investigation on IL-32 signaling pathways may contribute to development a more effective treatment of endometriosis.
STUDY FUNDING/COMPETING INTEREST(S):
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant number: HI16C1682). None of the authors has anything to disclose.
Best Pract Res Clin Obstet Gynaecol. 2018 Feb 21.
Obstetrical outcome in women with endometriosis including spontaneous hemoperitoneum and bowel perforation: a systematic review.
Increasing evidence suggests that pregnant women with endometriosis have a higher risk of adverse obstetrical complications. The aim of this study was to systematically review the existing literature on this aspect. A PubMed/MEDLINE search was performed from its inception until September 2017 for studies on adverse obstetrical complications in pregnant women with endometriosis, including: preeclampsia, preterm birth, small for gestational age (SGA), antepartum hemorrhage, spontaneous hemoperitoneum, spontaneous bowel perforation, preterm birth, cesarean delivery, stillbirth and postpartum hemorrhage. Overall, the results showed an increased risk of preterm delivery, antepartum hemorrhage, delivery by cesarian section, and the rare complications of spontaneous hemorrhage in pregnancy and spontaneous bowel perforation. There is no firm evidence for any increased risk of preeclampsia, having a child born small for gestational age, stillbirth, or postpartum hemorrhage. In conclusion, pregnant patients with endometriosis should be offered special clinical attention.
Obstet Gynecol Sci. 2018 Mar;61(2):261-266.
Postoperative outcomes of natural orifice transluminal endoscopic surgery-assisted vaginal hysterectomy and conventional laparoscopic-assisted vaginal hysterectomy: a comparative study.
The present study aimed to determine the differences in outcomes between natural orifice transluminal endoscopic surgery-assisted vaginal hysterectomy (NAVH) and conventional laparoscopy-assisted vaginal hysterectomy (LAVH).
We retrospectively reviewed the charts of patients who between July 2012 and September 2015, were diagnosed as having benign uterine disease such as uterine myoma, endometriosis, or adenomyosis and managed via NAVH or LAVH in a single-center (Eulji University Hospital). Data such as age, body weight, height, parity, operation time, intra/post-operative complications, and uterus weight were obtained from the clinical charts. NAVH and LAVH recipients were matched 1:3 in terms of baseline characteristics, and the 2 groups were compared regarding surgical outcomes.
Of the 160 patients with benign uterine disease included in the present study. Forty received NAVH and remaining 120 received LAVH. There were significant differences between the groups regarding operation time and hemoglobin change. Notably, although the operation time was shorter for LAVH, hemoglobin change was lower for NAVH. Additionally, although maximum hospitalization duration was shorter for LAVH, the average length of hospitalization was similar between NAVH and LAVH. There were no significant differences between the groups in terms of other variables.
NAVH may become a new alternative surgical method of choice for hysterectomy, as it represents a clinically feasible and safe approach; moreover is superior to LAVH in terms of bleeding loss.
Fertil Steril. 2018 Mar;109(3):380-388.e1.
Symptoms and classification of uterine adenomyosis, including the place of hysteroscopy in diagnosis.
Where histology used the presence of glands and/or stroma in the myometrium as pathognomonic for adenomyosis, imaging uses the appearance of the myometrium, the presence of striations, related to the presence of endometrial tissue within the myometrium, the presence of intramyometrial cystic structures and the size and asymmetry of the uterus to identify adenomyosis. Preliminary reports show a good correlation between the features detected by imaging and the histological findings. Symptoms associated with adenomyosis are abnormal uterine bleeding, pelvic pain (dysmenorrhea, chronic pelvic pain, dyspareunia), and impaired reproduction. However a high incidence of existing comorbidity like fibroids and endometriosis makes it difficult to attribute a specific pathognomonic symptom to adenomyosis. Heterogeneity in the reported pregnancy rates after assisted reproduction is due to the use of different ovarian stimulation protocols and absence of a correct description of the adenomyotic pathology. Current efforts to classify the disease contributed a lot in elucidated the potential characteristics that a classification system should be relied on. The need for a comprehensive, user friendly, and clear categorization of adenomyosis including the pattern, location, histological variants, and the myometrial zone seems to be an urgent need. With the uterus as a possible unifying link between adenomyosis and endometriosis, exploration of the uterus should not only be restricted to the hysteroscopic exploration of the uterine cavity but in a fusion with ultrasound.
Fertil Steril. 2018 Mar;109(3):389-397.
Role of transvaginal sonography and magnetic resonance imaging in the diagnosis of uterine adenomyosis.
The aim of the present review, conducted according to PRISMA statement recommendations, was to evaluate the contribution of transvaginal sonography (TVS) and magnetic resonance imaging (MRI) to diagnose adenomyosis. Although there is a lack of consensus on adenomyosis classification, three subtypes are described, internal, external adenomyosis, and adenomyomas. Using TVS, whatever the subtype, pooled sensitivities, pooled specificities, and pooled positive likelihood ratios are 0.72-0.82, 0.85-0.81, and 4.67-3.7, respectively, but with a high heterogeneity between the studies. MRI has a pooled sensitivity of 0.77, specificity of 0.89, positive likelihood ratio of 6.5, and negative likelihood ratio of 0.2 for all subtypes. Our results suggest that MRI is more useful than TVS in the diagnosis of adenomyosis. Further studies are required to determine the performance of direct signs (cystic component) and indirect signs (characteristics of junctional zone) to avoid misdiagnosis of adenomyosis.
Nutrition. 2018 May;49:24-31.
Vitamin D deficiency and high serum IL-6 concentration as risk factors for tubal factor infertility in Chinese women.
The aim of this study was to investigate the relationship between 25-hydroxyvitamin-D [25(OH)D] and female infertility and to further explore the role of inflammatory cytokines.
We recruited 356 infertile women diagnosed with tubal factor infertility (TFI) or polycystic ovary syndrome (PCOS) or endometriosis, as well as 180 fertile women. Serum concentrations of 25(OH)D, interleukin (IL)-6, IL-1 β, and interferon-α were measured.
The 25(OH)D concentration in TFI women was the lowest (16.9 ng/mL) and was significantly different from that in the fertile women (19.4 ng/mL; P <0.05)]; whereas women with TFI had higher IL-6 concentrations. After adjusting for confounders, 25(OH)D deficiency presented a risk factor for TFI (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.5-11.3). There was a dose-effect relation between IL-6 tertiles and TFI: the higher the IL-6, the higher the risk for TFI (middle versus low: OR, 3.7; 95% CI, 1.5-9.5; high versus low: OR, 13.2; 95% CI, 4.8-36.4). IL-6 showed a negative correlation with 25(OH)D (r = -0.19). Women with both high IL-6 and low 25(OH)D had the highest risk for TFI (OR, 10.6; 95% CI, 4.2-26.3).
Both vitamin D deficiency and high serum IL-6 concentration are risk factors for TFI. Serum 25(OH)D concentration was significantly and negatively correlated with serum IL-6. There was an interaction between IL-6 and 25(OH)D for the risk for TFI-related infertility. We hypothesized that vitamin D might reduce the risk for TFI through suppressing the production of IL-6.
Arch Gynecol Obstet. 2018 Mar 23.
The role of complement components C1q, MBL and C1 inhibitor in pathogenesis of endometriosis.
The purpose of the work was to evaluate possible associations between the complement components C1q, mannose-binding lectin (MBL) and C1 inhibitor (C1INH) with pathogenesis of endometriosis.
Concentrations of C1q, MBL and C1INH were measured by ELISA in peritoneal fluid (PF) in 80 women with or without endometriosis.
Significantly higher PF levels of C1q, MBL and C1INH in women with endometriosis compared to control group were observed (p < 0.0001). A higher concentration of the studied parameter was found in PF of women at the early stage of the disease, as compared to women with advanced endometriosis (p < 0.0001).
Our research suggests that in the peritoneal cavity in women with endometriosis there are abnormal regulations of both the classical and lectin pathways of the complement system. This can suggest impairments in purification of peritoneal cavity from ectopic endometrial cells and augmented local inflammation in endometriosis patients.
Eur J Obstet Gynecol Reprod Biol. 2018 Mar 15;224:108-116.
Intraoperative enhanced imaging for detection of endometriosis: A systematic review of the literature.
The diagnosis of peritoneal endometriosis during laparoscopy may be difficult due to the polymorphic aspects of the lesions. Enhanced imaging using contrast agents has potential to provide a better identification of peritoneal endometriosis. The aim of this systematic review is to provide an overview of the literature on what is known about the intraoperative laparoscopic visual enhancement of peritoneal endometriosis using contrast agents. A systematic review was done of studies about enhanced imaging during laparoscopy for endometriosis using contrast agents. Clinical studies which contained a description of imaging with a contrast agent and also reported visual findings of endometriosis during laparoscopy, were included. Nine suitable studies were identified. Intraoperative visualization of endometriosis was analyzed with or without histologic confirmation. Four studies evaluated 5-aminolevulinic acid-induced fluorescence (5-ALA), 1 study evaluated indigo carmine, 2 studies evaluated methylene blue (MB), 1 study evaluated indocyanine green (ICG) and 1 study evaluated so-called bloody peritoneal fluid painting. All studies, with a combined total of 171 included patients, showed potential of enhanced visibility of endometriosis using contrast agents. A combined total of 7 complications, all related to the use of 5-ALA, were reported. We conclude that the use of contrast-based enhanced imaging during laparoscopy is promising and that it can provide a better visualization of peritoneal endometriosis. However, based on the limited data no technique of preference can yet be identified.
J Gynecol Obstet Hum Reprod. 2018 Mar 21.
About a case of traumatic separation of the cervix from the uterine corpus, diagnosed in a context of infertility.
This article reports a case of cervico-isthmic disjunction unnoticed during childhood, diagnosed in a context of primary infertility and endometriosis, and surgically treated. It is an uncommon condition. The diagnosis is most often made as part of an assessment of primary amenorrhea in a young woman with a history of severe pelvic trauma. It is suspected after imaging assessment and confirmed intraoperatively. The treatment consists in an anastomosis between the cervix and the uterine body, after individualizing these two structures, around a drain guiding healing. After this surgery, multiple pregnancies have been successfully carried out.
Best Pract Res Clin Obstet Gynaecol. 2018 Feb 14.
Pathogenesis of endometriosis: Interaction between Endocrine and inflammatory pathways.
Despite an estimated prevalence of 11% in women and plausible historical descriptions dating back to the 17th century, the etiology of endometriosis remains poorly understood. Classical theories of the histological origins of endometriosis are reviewed below. Clinical presentations are variable, and signs and symptoms do not correlate well with the extent of disease. In this summary, we have attempted to synthesize the growing evidence that hormonal and immune factors conspire to activate a local inflammatory microenvironment that encourages endometriosis to persist and elaborate mediators of its two cardinal symptoms: pain and infertility. Surprisingly, in the search for novel therapeutics for medical treatment of endometriosis, some compounds appear to have dual pharmacological functions, simultaneously modifying the endocrine and immune system facets of this complex gynecologic syndrome. We predict that these lead drugs will provide more therapeutic choices for patients in the future.
Gynecol Surg. 2018;15(1):8.
Surgical outcomes of laparoscopic hysterectomy with concomitant endometriosis without bowel or bladder dissection: a cohort analysis to define a case-mix variable.
Pelvic endometriosis is often mentioned as one of the variables influencing surgical outcomes of laparoscopic hysterectomy (LH). However, its additional surgical risks have not been well established. The aim of this study was to analyze to what extent concomitant endometriosis influences surgical outcomes of LH and to determine if it should be considered as case-mix variable.
A total of 2655 LH’s were analyzed, of which 397 (15.0%) with concomitant endometriosis. For blood loss and operative time, no measurable association was found for stages I (n = 106) and II (n = 103) endometriosis compared to LH without endometriosis. LH with stages III (n = 93) and IV (n = 95) endometriosis were associated with more intra-operative blood loss (p = < .001) and a prolonged operative time (p = < .001) compared to LH without endometriosis. No significant association was found between endometriosis (all stages) and complications (p = .62).
The findings of our study have provided numeric support for the influence of concomitant endometriosis on surgical outcomes of LH, without bowel or bladder dissection. Only stages III and IV were associated with a longer operative time and more blood loss and should thus be considered as case-mix variables in future quality measurement tools.
Best Pract Res Clin Obstet Gynaecol. 2018 Feb 8.
Patient-centeredness and endometriosis: Definition, measurement, and current status.
The patient-centeredness of care is important for health care quality, especially because it was recently associated with health-related quality of life, which is increasingly being recognized as the ultimate outcome parameter of health care. Therefore, insight into the definition, measurement, and current status of the patient-centeredness of clinics is important for all health care professionals caring for patients with endometriosis. The definition of patient-centered endometriosis care is based on research into the most common preferences, needs, and values of patients with endometriosis and can be summarized in ten dimensions. One valid and reliable questionnaire exists, the ENDOCARE questionnaire, which allows measuring the patient-centeredness status of an endometriosis clinic. This questionnaire has been used to benchmark centers in different countries and has allowed the identification of ten targets for improving the patient-centeredness of endometriosis care. The next step would be to use the ENDOCARE questionnaire before and after an improvement project.
Indian J Surg. 2018 Feb;80(1):48-53.
Incidental Findings in Routine Histopathological Examination of Appendectomy Specimens; Retrospective Analysis of 1970 Patients.
Diseases and tumors of the appendix vermiformis are very rare, except for acute appendicitis. This study aimed to examine rare findings in the histopathologic examinations of specimens of patients undergoing appendectomy due to the diagnosis of acute appendicitis. The files of 1970 patients undergoing appendectomy due to the diagnosis of acute appendicitis between March 2012 and March 2016 were retrospectively investigated. Rare findings were found in 59 (3 %) patients, and these were evaluated in detail. Patients’ age, gender, pathology reports, and postoperation follow-ups were recorded. The rare histopathological findings of 59 patients were examined. Of these, 31 were female (52.5 %) and 28 were male (47.5 %). The average age was 33.1 ± 18.2 years. The unusual findings were as follows: 16 fibrous obliteration, 11 Enterobius vermicularis, 2 schistosomiasis, 3 appendiceal neuroma, 2 granulomatous appendicitis, 1 Crohn’s disease, 3 chronic appendicitis, 1 endometriosis, 2 hyperplastic polyps, 9 mucinous cystadenoma (+mucocele), 8 carcinoid tumors, and 1 lymphoma. All of the malignant tumors were localized in the distal end of the appendix, and all of the patients were treated with appendectomy. Patients with parasitic diseases also underwent anthelmintic treatment, while chemotherapy was administered to the patient with lymphoma. All of the patients diagnosed with malignancy were alive reported no problems at their follow-ups. Although all of the appendectomy samples were normal macroscopically, data from this study suggest that all specimens should be sent for routine investigation.
Reprod Sci. 2018 Jan 1
Serum MicroRNA Biomarkers Regulated by Simvastatin in a Primate Model of Endometriosis.
Endometriosis is a chronic inflammatory and estrogen-dependent disease that causes pain and infertility in reproductive-aged women. Due to the delay in diagnosis, there is a pressing need for accurate biomarkers. Detection of serum noncoding RNA molecules such as microRNAs (miRNAs) shows promise as a noninvasive diagnostic strategy; we previously identified miRNAs that are highly sensitive and specific biomarkers for the disease. In this study, we investigate the expression of these miRNAs in a nonhuman primate model of endometriosis. As part of a pilot study evaluating simvastatin for the treatment of endometriosis, the disease was induced in 16 baboons by induction laparoscopy and the animals were divided into 2 groups. One group was treated with simvastatin for 90 days, while the second group received vehicle only. Endometriosis was evaluated after 3 months by laparoscopy. Serum samples were analyzed for 9 circulating miRNAs using quantitative real time-polymerase chain reaction, focusing on the miRNAs we found to be dysregulated in human endometriosis. In the simvastatin-treated endometriosis group, levels of miR-150-5p and miR-451a were decreased, while miR-3613-5p levels were increased compared to the untreated endometriosis group. The changes in circulating miRNA expression patterns parallel our previous results in human patients and show that specific miRNAs correlate with endometriosis severity and reverted toward control expression levels after simvastatin treatment. This is the first report showing serum miRNA expression normalized in response to endometriosis treatment, supporting the potential for this class of biomarkers to be used both to diagnose endometriosis and to monitor its progression and response to therapy.
Reprod Sci. 2018 Jan 1:1933719118766256. doi: 10.1177/1933719118766256. [Epub ahead of print]
G-Protein-Coupled Receptor CXCR7 Is Overexpressed in Human and Murine Endometriosis.
Endometriosis is a chronic inflammatory disease. Dysfunctional regulation of chemokines and chemokine receptors is a crucial aspect of endometriosis pathogenesis. Chemokine G-protein-coupled receptors (GPCRs) are important drug targets that regulate inflammation and immunity. Recently, CXCR7, a C-X-C motif containing GPCR, has been identified as a receptor for chemokine ligand CXCL12, one of the best characterized chemokines for cell trafficking, angiogenesis, and cell proliferation in cancer and inflammation. Here, we investigated the expression and localization of CXCR7 in human endometriosis and a murine model of the disease. Normal endometrial epithelium and stroma showed undetectable or very low expression of CXCR7, without any significant changes across phases of the menstrual cycle in humans. CXCR7 is significantly upregulated in endometriosis, showing higher staining in glands and in associated vessels. The mouse model recapitulated the human findings. In conclusion, overexpression of CXCR7 in different cellular populations of endometriosis microenvironment may play a role in the pathogenesis and represent a novel target for treatment.
Reprod Sci. 2018 Jan 1
25-Hydroxyvitamin D Serum Levels and Endometriosis: Results of a Case-Control Study.
The immunomodulatory, anti-inflammatory, and antiproliferative properties of vitamin D have laid the basis for a possible function of this prohormone in the pathogenesis of endometriosis. The aim of this case-control study was to investigate vitamin D status, by measuring 25-hydroxyvitamin D [25(OH)D] serum levels, in women with and without endometriosis. Only Italian women of Caucasian origin aged between 18 and 45 years were deemed eligible. Enrollment was limited to the period October to May. Cases and controls were matched for month of recruitment and secondarily for age and parity. Overall, 434 women were enrolled (endometriosis n = 217; controls n = 217). The group of cases included 127 women with ovarian endometrioma and 90 patients with deep endometriosis. Mean (standard deviation) levels of 25(OH)D in women with and without endometriosis were 17.9 (7.0) ng/mL and 18.4 (7.6) ng/mL, respectively ( P = .46). Analyzing the two endometriosis subgroups separately, no statistically significant differences emerged (18.7 [7.4] ng/mL in deep endometriosis group vs 17.3 [6.6] ng/mL in women with ovarian endometrioma; P = .14). Comparing the subgroup of women with deep endometriosis with paired controls, no differences occurred (18.7 [7.4] ng/mL vs 18.5 [7.7] ng/mL, P = .80). Similar data emerged when performing the same analysis for ovarian endometriomas (17.4 [6.6] ng/mL vs 18.3 [7.6] ng/mL, P = .23). The results of the present case-control study do not support an association between serum vitamin D levels and different phenotypes of endometriosis.
Reprod Sci. 2018 Jan 1
Macrophage Migration Inhibitory Factor Receptor, CD74, is Overexpressed in Human and Baboon ( Papio Anubis) Endometriotic Lesions and Modulates Endometriotic Epithelial Cell Survival and Interleukin 8 Expression.
CD74 is the primary receptor for macrophage migration inhibitory factor (MIF). Although expression of MIF has been described in endometriotic lesions, the cellular localization and function of the MIF receptor, CD74, are poorly understood. To further explore the role of CD74 in the pathophysiology of endometriosis, we utilized specimens from women with diagnostically confirmed endometriosis, women with no signs or symptoms of endometriosis (controls), and 8 baboons with experimentally induced endometriosis. Compared to eutopic endometrium from women with endometriosis, CD74 transcript expression was significantly increased in endometriotic lesion tissue. Similarly, cellular expression of CD74 was significantly greater in ectopic lesion tissue compared to paired eutopic endometrium, which both expressed greater CD74 expression compared to eutopic endometrium from control patients. Localization of CD74 was predominant to epithelial cells of ectopic and matched eutopic endometrium and was not influenced by the stage of the menstrual cycle. Eutopic endometrium from control patients did not express detectable levels of CD74 protein by immunohistochemistry. This pattern of expression and CD74 protein localization could be recapitulated in endometriotic lesion tissue from baboons with experimentally induced disease. Transfection of the endometriotic epithelial cell lines, 12Z with CD74 short hairpin RNA (shRNA), resulted in a significant decrease in CD74 protein expression, which was associated with a significant reduction in cellular proliferation as well as the expression of the prosurvival cytokine interleukin 8. Together, these data support the hypothesis that CD74 is elevated in endometriotic lesion tissue and may contribute to the pathogenesis of endometriosis by promoting cell survival.
Reprod Sci. 2018 Jan 1
Epigenetic Dynamics of HOXA10 Gene in Infertile Women With Endometriosis.
Endometriosis, which has been considered an epigenetic disease, is a prevalent gynecological disorder worldwide. With an emphasis on changes in the HOXA10 gene expression of the endometrium of women with endometriosis, the aim of this study was to investigate HOXA10 gene expression and its correlation with the epigenetic characteristics of the specific promoter region of the gene in the eutopic and ectopic endometrium of women with endometriosis. Thirty-six patients and 21 healthy fertile women were recruited as participants of this study. In this study group, chromatin immunoprecipitation and real-time polymerase chain reaction technique were performed to quantify the epigenetic profile of HOXA10, parallel to its expression. During the secretory phase in eutopic tissues, reduction in HOXA10 gene expression was identified along with lower acetylation and higher methylation of H3K9 as well as higher incorporation of MeCP2 on the HOXA10 gene promoter. In contrast with control group, studies of ectopic endometriotic lesions in the secretory phase demonstrate a correlation between induction of HOXA10 gene and higher levels of H3K9ac, H3K27me3, and H3K4me3 in the promoter region of the HOXA10 gene. Further distinctions from the control group were revealed in the proliferative phase of the ectopic endometrium, where upregulation of HOXA10 coincided with lower incorporation of MeCP2 and higher levels of H3K4me3 in the promoter region. Since it is well known that aberrant expression of HOXA10 is involved in pathogenesis of the endometrium, our data emphasized the epigenetic role of this gene aberration related to clinical pathophysiology of endometriosis.
Case Rep Womens Health. 2017 Sep 8;16:1-3.
A case of uterus-like mass of the ovary associated with endometriosis.
- Coelomic metaplasia is considered to be one of the mechanisms resulting in endometriosis.•Intense ceolomic metaplasia resulted in a uterine like mass (ULM) acquiring the structural integrity of a miniature uterus.•ULM might be considered a rare manifestation in the spectrum of endometriosis development.
Chin J Integr Med. 2018 Mar 28.
Strategies for Activating Blood Circulation-Regulating Gan (Liver)-Tonifying Shen (Kidney) Sequential Therapy of Endometriosis-Associated Infertility.
Endometriosis (EM) is a major cause of infertility and has a complex pathogenesis, which brings severe challenges in both clinical treatment and scientific research. Current clinical research focuses on the difficult problem of improving the pregnancy rate of EM patients. Our studies found that Chinese medicine has significant advantages in terms of improving the pregnancy rate of EM patients.
Syst Biol Reprod Med. 2018 Mar 29:1-4.
Follicular fluid levels of anti-Müllerian hormone, insulin-like growth factor 1 and leptin in women with fertility disorders.
Anti-Müllerian hormone (AMH), insulin-like growth factor 1 (IGF1) and leptin are produced in the granulosa cells of follicles and play an important role in the growth and maturation of follicles. The aim of our study was to monitor AMH, IGF1 and leptin levels in a group of healthy women and compare them to a group of women with fertility disorders. The second aim was the evaluation of biomarker levels in relation to the identified cause of infertility. Totally, 146 females were enrolled into our study. Seventy-two healthy controls and seventy-four females with fertility disorders were divided into four subgroups: anovulation, endometriosis, fallopian tube damage, unknown reason. IGF1 was the only biomarker with significantly lower levels throughout the entire group with fertility disorders. We did not identify any statistically significant differences for AMH and leptin. Regarding subgroups, significant differences were only observed in the group of anovulatory women. AMH and leptin showed higher levels while IGF1 showed lower levels. In conclusion, levels of AMH, IGF1 and leptin found in follicular fluid are sensitive markers for anovulatory fertility disorders. AMH, IGF1 and leptin levels in follicular fluid have no relation to the fertility disorders caused by endometriosis, fallopian tube damage or disorders with unknown etiology.
Oncotarget. 2018 Feb 22;9(19):14754-14763.
Affinity-purified DNA-based mutation profiles of endometriosis-related ovarian neoplasms in Japanese patients.
Endometriosis-related ovarian neoplasms (ERONs) have recently attracted considerable attention; however, the prevalence and patterns of ARID1A and POLE mutations in ERONs have not been studied in detail. The aim of this study was to investigate not only the carcinogenesis of ERONs, but also the prognostic significance of several gene mutations in this cohort. We used DNA purified from only tumor epithelial cells, from which fibroblasts were removed, using a specific method we called “liquid microdissection”.
Tissue samples from 22 ovarian carcinomas (13 endometrioid, and nine clear cell) were used. Tumor cells were isolated using a cell sorting system and DNA was purified from tumor epithelial cells. Nucleotide sequencing was conducted to analyze the mutational status of ARID1A, p53, PTEN, POLE, PIK3CA, and KRAS.
In ERONs, the frequencies of somatic mutations in ARID1A, p53, POLE, PTEN, PIK3CA, and KRAS were 19/20 (95.0%), 7/19 (36.8%), 9/22 (40.9%), 13/19 (68.4%), 3/19 (15.8%), and 1/9 (11.1%). The frequency of ARID1Amutations was significantly higher than that reported previously. Kaplan-Meier survival analysis revealed that mutations in all genes, including POLE, were not associated with patient prognosis in our Japanese cohort.
Our results suggest that the frequency of ARID1A mutations in ERONs may be higher than that previously reported. In addition, the “liquid microdissection” method that we chose for DNA purification could be used to obtain high-quality sequencing results. The findings suggest that ARID1A mutations represent the basis of ERON carcinogenesis; other subsequent gene mutations may result in the progression of carcinogenesis.
Arch Gynecol Obstet. 2018 Mar 30.
Placenta previa and placental abruption after assisted reproductive technology in patients with endometriosis: a systematic review and meta-analysis.
Recent evidence suggests that assisted reproductive technology (ART) increases the risk of adverse pregnancy outcomes, including placental disorders. Similarly, endometriosis resulted detrimental on placenta previa. However, up to 50% of women with endometriosis suffer from infertility, thus requiring ART. The aim of our metanalysis is to compare women with and without endometriosis undergoing ART in terms of placenta disorders events, to establish if ART itself or endometriosis, as an indication to ART, increases the risk of placenta previa.
Literature searches were conducted in January 2018 using electronic databases (PubMed, Medline, Scopus, Embase, Science Direct, and the Cochrane Library Scopus). Series comparing pregnancy outcome after ART in women with and without endometriosis were screened and data on placenta previa and placental abruption were extracted.
Five retrospective case-control studies met the inclusion criteria. The meta-analysis revealed that endometriosis is associated with an increased risk of placenta previa in pregnancies achieved through ART (OR 2.96 (95% CI 1.25-7.03); p = 0.01, I2 =69%, random-effect model). No differences in placental abruption incidence were found (OR 0.44 (95% CI 0.10-1.87); p = 0.26, I2 = 0%, fixed-effect model).
Patients with endometriosis undergoing ART may have additional risk of placenta previa. Despite the inability to determine if endometriosis alone or endometriosis plus ART increase the risk, physicians should be aware of the potential additional risk that endometriosis patients undergoing ART harbor.
Surg Endosc. 2018 Mar 30. doi: 10.1007/s00464-018-6165-5. [Epub ahead of print]
Validity evidence for procedural competency in virtual reality robotic simulation, establishing a credible pass/fail standard for the vaginal cuff closure procedure.
The use of robotic surgery for minimally invasive procedures has increased considerably over the last decade. Robotic surgery has potential advantages compared to laparoscopic surgery but also requires new skills. Using virtual reality (VR) simulation to facilitate the acquisition of these new skills could potentially benefit training of robotic surgical skills and also be a crucial step in developing a robotic surgical training curriculum. The study’s objective was to establish validity evidence for a simulation-based test for procedural competency for the vaginal cuff closure procedure that can be used in a future simulation-based, mastery learning training curriculum.
Eleven novice gynaecological surgeons without prior robotic experience and 11 experienced gynaecological robotic surgeons (> 30 robotic procedures) were recruited. After familiarization with the VR simulator, participants completed the module ‘Guided Vaginal Cuff Closure’ six times. Validity evidence was investigated for 18 preselected simulator metrics. The internal consistency was assessed using Cronbach’s alpha and a composite score was calculated based on metrics with significant discriminative ability between the two groups. Finally, a pass/fail standard was established using the contrasting groups’ method.
The experienced surgeons significantly outperformed the novice surgeons on 6 of the 18 metrics. The internal consistency was 0.58 (Cronbach’s alpha). The experienced surgeons’ mean composite score for all six repetitions were significantly better than the novice surgeons’ (76.1 vs. 63.0, respectively, p < 0.001). A pass/fail standard of 75/100 was established. Four novice surgeons passed this standard (false positives) and three experienced surgeons failed (false negatives).
Our study has gathered validity evidence for a simulation-based test for procedural robotic surgical competency in the vaginal cuff closure procedure and established a credible pass/fail standard for future proficiency-based training.
J Pathol. 2018 Mar 31.
Independent development of endometrial epithelium and stroma within the same endometriosis.
The pathogenesis of endometriosis, a common benign but debilitating disease in women, remains elusive. The currently held stem cell theory posits that circulating progenitor/stem cells are deposited outside the uterus where they differentiate into endometrial stroma and glandular tissue to establish endometriosis. Fundamental to testing this hypothesis is to elucidate the evolution of both tissue types. Here, we applied droplet digital PCR to analyze synonymous and missense somatic passenger mutations, which are neutral with respect to clonal selection, among six non-superficial endometriotic lesions. We found that among 19 mutations sequenced, all were significantly enriched in epithelial but not in stromal components of every lesion examined. Our data indicate that the evolution of non-superficial endometriosis is complex, in that epithelium is clonal and its development is independent of stroma, providing new insight into the genesis of endometriosis.
Histopathology. 2018 Mar 31.
Absence of KRAS hotspot mutations in endometriosis of Korean patients.
Endometriosis is a condition in which endometrial epithelial and stromal tissue is present outside of the uterus. It involves ovaries, fallopian tubes, tissue lining the pelvis and even beyond pelvic organs. While the exact cause of endometriosis remains unknown, many theories have been presented including retrograde menstruation (implantation) and stem cell theories.1 Endometriosis includes three subtypes: superficial peritoneal endometriosis, ovarian endometriosis and deep infiltrating endometriosis (DIE),2 although there is a lot of overlap between these 3 categories and they are not well defined. This article is protected by copyright. All rights reserved.
Fertil Steril. 2018 Apr;109(4):685-690.
Prevalence of migraines in adolescents with endometriosis.
To determine the prevalence and experience of migraines in adolescents with surgically confirmed endometriosis compared with those without endometriosis.
Cross-sectional study conducted within The Women’s Health Study: From Adolescence to Adulthood-an ongoing longitudinal cohort.
Boston Center for Endometriosis.
Adolescent females enrolled November 2012 through November 2016. The case group included adolescents surgically diagnosed with endometriosis. The control group included adolescents without endometriosis, recruited from the local community and clinics.
MAIN OUTCOME MEASURE(S):
An extensive online health questionnaire regarding medical history, lifestyle, medication use, anthropometrics, and symptom experience and treatments. Migraine diagnosis was self-reported. Migraine pain and noncyclic pelvic pain severity were rated using an 11-point numerical rating scale. Cyclic pelvic pain was categorized.
Adolescents with endometriosis were more likely to experience migraines (69.3%) than those without endometriosis (30.7%) (multivariable odds ratio = 4.77, 95% confidence interval 2.53, 9.02). For each 1-point increase in the migraine numerical rating scale, the odds of endometriosis increased by 22% (multivariable odds ratio = 1.22, 95% confidence interval 1.03, 1.44; Ptrend = .02). Among those with endometriosis, age of menarche was associated inversely with the odds of migraines. Participants with endometriosis and migraines have more dysmenorrhea than those without migraines.
Adolescents with endometriosis are more likely to experience migraines than adolescents without endometriosis. A linear relationship exists between migraine pain severity and the odds of endometriosis, suggesting heightened pain sensitivity for adolescents with endometriosis. Due to the strong correlation, patients who present with either condition should be screened for comorbidity to maximize the benefits of care.
Fertil Steril. 2018 Apr;109(4):675-684.e2.
Micro-RNA profile and proteins in peritoneal fluid from women with endometriosis: their relationship with sterility.
To define the microRNA (miRNA) profile and its relationship with cytokines content in peritoneal fluid (PF) from endometriosis patients.
University hospital, research institute.
One hundred twenty-six women with endometriosis (EPF) and 45 control women (CPF).
MAIN OUTCOMES MEASURE(S):
MiRNA arrays were prepared from six EPF and six CPF. Quantitative reverse transcription-polymerase chain reaction validation of nine selected miRNAs (miR-29c-3p, -106b-3p, -130a-3p, -150-5p, -185-5p, -195-5p, -451a, -486-5p, and -1343-5p) was performed. Vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1), urokinase plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1), matrix metalloproteinase-3 (MMP3), tissue inhibitor of metalloproteinases type 1 (TIMP-1), interleukin (IL)-6, IL-8, IL-17A, macrophage inflammatory protein 1β (MIP1beta), platelet-derived growth factor α-polypeptide A, and regulated on activation, normal T cell expressed and secreted (RANTES) were quantified by ELISA and MILLIPLEX.
MiRNA arrays showed 126 miRNAs differentially expressed (fold change ±1.2) (78 down-regulated, 48 up-regulated) in EPF. Validation showed higher levels of miR-106b-3p, -451a, -486-5p, IL-6, IL-8, uPA, and TIMP-1 in EPF. In menstrual phase, EPF presented up-regulation of miR-106b-3p, -130a-3p, -150-5p, -185-5p, -451a, -486-5p, VEGF-A, IL-8, MIF 1β, uPA, and PAI-1 compared with other phases; however, CPF did not. MiRNA-486-5p was up-regulated in sterile EPF compared with sterile controls, and VEGF-A, IL-8, and TIMP-1 were increased in sterile and fertile EPF compared with fertile CPF.
MiRNAs seem to be involved in the peritoneal alterations in endometriosis, suggesting new mechanisms by which ectopic lesions could implant in endometriosis patients; and to serve as biomarkers for fertility outcome prediction.
Cancer Med. 2018 Apr 2.
Genetic overlap between endometriosis and endometrial cancer: evidence from cross-disease genetic correlation and GWAS meta-analyses.
Painter JN1, O’Mara TA1, Morris AP2,3, Cheng THT4, Gorman M4, Martin L4, Hodson S5, Jones A4, Martin NG1, Gordon S1, Henders AK6, Attia J7,8, McEvoy M8, Holliday EG7,8, Scott RJ9,10, Webb PM11, Fasching PA12,13, Beckmann MW12, Ekici AB14, Hein A12, Rübner M12, Hall P15, Czene K15, Dörk T16, Dürst M17, Hillemanns P16, Runnebaum I17, Lambrechts D18,19, Amant F20, Annibali D20, Depreeuw J19,20,21, Vanderstichele A20, Goode EL22, Cunningham JM23, Dowdy SC24, Winham SJ22, Trovik J25,26, Hoivik E25,26, Werner HMJ25,26, Krakstad C25,26, Ashton K7,10,27, Otton G28, Proietto T28, Tham E29,30, Mints M31, Ahmed S32, Healey CS32, Shah M32, Pharoah PDP32,33, Dunning AM32, Dennis J33, Bolla MK33, Michailidou K33,34, Wang Q33, Tyrer JP32, Hopper JL35, Peto J36, Swerdlow AJ37,38, Burwinkel B39,40, Brenner H41,42,43, Meindl A44, Brauch H43,45,46, Lindblom A29, Chang-Claude J47,48, Couch FJ23, Giles GG35,49, Kristensen VN50,51,52, Cox A53, Zondervan KT54, Nyholt DR1,55, MacGregor S1, Montgomery GW1,6, Tomlinson I4, Easton DF32,33, Thompson DJ33, Spurdle AB1.
Epidemiological, biological, and molecular data suggest links between endometriosis and endometrial cancer, with recent epidemiological studies providing evidence for an association between a previous diagnosis of endometriosis and risk of endometrial cancer. We used genetic data as an alternative approach to investigate shared biological etiology of these two diseases. Genetic correlation analysis of summary level statistics from genomewide association studies (GWAS) using LD Score regression revealed moderate but significant genetic correlation (rg = 0.23, P = 9.3 × 10-3 ), and SNP effect concordance analysis provided evidence for significant SNP pleiotropy (P = 6.0 × 10-3) and concordance in effect direction (P = 2.0 × 10-3 ) between the two diseases. Cross-disease GWAS meta-analysis highlighted 13 distinct loci associated at P ≤ 10-5 with both endometriosis and endometrial cancer, with one locus (SNP rs2475335) located within PTPRD associated at a genomewide significant level (P = 4.9 × 10-8 , OR = 1.11, 95% CI = 1.07-1.15). PTPRD acts in the STAT3 pathway, which has been implicated in both endometriosis and endometrial cancer. This study demonstrates the value of cross-disease genetic analysis to support epidemiological observations and to identify biological pathways of relevance to multiple diseases.
Health Care Women Int. 2018 Apr 2:1-26.
The construction and validation of the Stellenbosch Endometriosis Quality of life measure (SEQOL).
In this paper, we describe the process of construction and validation of a health-related quality of life (HRQOL) measure for patients with endometriosis. The items in the measure were initially constructed, edited and reduced using a consultative process with endometriosis experts. We then determined the test reliability, validity and factor structure of the measure by administering the measure and several other measures to 203 patients with endometriosis. The 35-item measure produced an eight-dimension factor structure. The measure and its subscales demonstrated excellent internal consistency reliability and promising validity.
J Minim Invasive Gynecol. 2018 Mar 30.
Surgical Excision Versus Ablation for Superficial Endometriosis Associated Pain: A Randomized Controlled Trial.
To compare surgical excision and ablation of endometriosis for treatment of chronic pelvic pain.
Canadian task force Category I – randomized clinical trial with 12-month follow-up.
Single academic tertiary care hospital.
Women with minimal to mild endometriosis undergoing laparoscopy.
Excision or ablation of superficial endometriosis at the time of robot-assisted laparoscopy.
MEASUREMENTS AND MAIN RESULTS:
Primary outcome was VAS scoring at baseline, six and twelve months for menstrual pain, non-menstrual pain, dyspareunia, dyschezia. Secondary outcomes included survey results at baseline, six and twelve months from the Short Form Health Survey (SF-12), Pelvic Organ Prolapse/Urinary Incontinence Sexual Function Questionnaire (PISQ-12) and the International Pelvic Pain Assessment. From December 2013 to October 2014, 73 patients were randomized intra-operatively to excision (n=37) or ablation (n=36) of endometriosis. Patients were followed at 6 and 12 months to evaluate the above outcomes. After ablation of endometriosis, dyspareunia (VAS scores) improved at 6 (mean change [MC]= -14.07; 95% Confidence Interval [CI] =(-25.93, -2.21); p=0.02) but improvement was not maintained at 12 months. Dysmenorrhea improved at 6 months (MC= -26.99; 95% CI=(-41.48, -12.50); p=<.001) and 12 months (MC= -24.15; 95% CI=(39.62, -8.68); p=0.003) with ablation. No significant changes were seen in VAS scores after excision at 6 or 12 months. When comparing ablation and excision, the only significant difference was a change in dyspareunia at 6 months (MC= -22.96 95% CI=(-39.06, -6.86); p=0.01).
Treatment with ablation improved dysmenorrhea at 6 and 12 months and improved dyspareunia at 6 months as compared to pre-operative data. However, only dyspareunia demonstrated a significant difference between ablation and excision. Excision and ablation showed similar effectiveness for the treatment of pain associated with superficial endometriosis with ablation showing more significant individual changes. Careful patient counseling regarding expectations of surgical intervention is vital in the management of endometriosis.
J Minim Invasive Gynecol. 2018 Mar 30.
Magnetic Resonance Imaging Guided High Intensity Focused Ultrasound is a Non-Invasive Treatment Modality for Patients with Abdominal Wall Endometriosis.
Two females (29 and 35 years of age) presented with an abdominal wall mass in close proximity to a caesarean scar. The main complaints consisted of pain at the site of the mass, with catamenial exacerbations. Clinical and imaging findings were consistent with abdominal wall endometriosis in both cases. First, hormonal treatment was started, which proved unsuccessful. Typically at this point the proposed treatment would be wide-surgical excision. Alternatively, MR-HIFU treatment was offered with the goal to diminish pain complaints non-invasively. Upon treatment both patients’ complaints diminished, although some cyclic pain persisted. Overall, these cases show that MR-HIFU can be used as a non-invasive treatment method to reduce complaints in patients with abdominal wall endometriosis.
Rev Bras Ginecol Obstet. 2018 Mar;40(3):115-120.
Female Sexual Function in Women with Suspected Deep Infiltrating Endometriosis.
To evaluate the quality of the sexual function of women with suspected deep infiltrating endometriosis.
A cross-sectional, observational and prospective study was conducted between May 2015 and August 2016, in which 67 patients with deep infiltrating endometriosis, suspected or diagnosed, were assessed for epidemiological and clinical characteristics, such as pain level through a visual analog scale (VAS), features of deep infiltrating endometriosis lesions and score on the Female Sexual Function Index (FSFI) before the onset of treatment. The statistical analysis was performed using the software STATA version 12.0 (StataCorp LLC, College Station, TX, USA) to compare the variables through multiple regression analysis.
The average age of the patients was 39.2 years old; most patients were symptomatic (92.5%); and the predominant location of the deep infiltrating lesions was on the rectosigmoid colon (50%), closely followed by the retrocervical region (48.3%). The median overall score on the FSFI was 23.4; in 67.2% of the cases the score was ≤ 26.5 (cutoff point for sexual dysfunction). Deep dyspareunia (p = 0.000, confidence interval [CI]: 0.64-0.83) and rectosigmoid endometriosis lesions (p = 0.008, CI: 0.72-0.95) showed significant correlation with lower FSFI scores, adjusted by bladder lesion, patients’ age and size of lesions. Deep dyspareunia (p = 0.003, CI: 0.49-0.86) also exhibited significant correlation with FSFI pain domain, adjusted by cyclic bowel pain, vaginal lesion and use of gonadotropin-releasing hormone (GnRH) analog. These results reflect the influence of deep dyspareunia on the sexual dysfunction of the analyzed population.
Most patients exhibited sexual dysfunction, and deep dyspareunia was the pelvic painful symptom that showed correlation with sexual dysfunction.
Zhonghua Fu Chan Ke Za Zhi. 2018 Mar 25;53(3):167-171.
[Role and clinical significance of coagulation and inflammatory factors in moderate and severe ovarian endometriosis].
Objective: To determine the levels of coagulation and inflammatory factors in women with moderate and severe ovarian endometriosis so as to investigate the possible role of coagulation and inflammatory factors in the pathogenesis, diagnosis and treatment of this disease. Methods: From June 2015 and June 2017, clinical data of 366 patients with pathologically diagnosed moderate and severe ovarian endometriosis (case group) and 244 patients with pathologically diagnosed benign ovarian cysts (control group) in Women’s Hospital of Zhejiang University School of Medicine were retrospectively analyzed. The levels of coagulation indicators, inflammatory factors and serum tumor markers were measured. Then, the values of these indicators in diagnosis of endometriosis were analyzed. Results:(1) The levels of plasma prothrombin time (PT) and thrombin time (TT) in patients with ovarian endometriosis [median: 12.8 s (range: 12.4-13.2 s) and 15.5 s (range: 15.1-15.9 s), respectively] were significantly shorter than those with benign ovarian cysts [median: 13.0 s (range: 12.5-13.4 s) and 15.7 s (range: 15.3-16.1 s), respectively; allP<0.01]. The levels of plasma fibrinogen (FIB) and D-dimer [D-D; median: 3.1 g/L (range: 2.8-3.5 g/L) and 0.9 mg/L (range: 0.6-2.1 mg/L) , respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.8 g/L (range: 2.6-3.2 g/L) and 0.6 mg/L (range: 0.4-1.2 mg/L), respectively; P=0.000]. Moreover, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio [PLR; median: 2.3 (range: 1.8-3.1) and 144 (range: 113-179), respectively] in patients with ovarian endometriosis were significantly higher than those with benign ovarian cysts [median: 2.1 (range: 1.6-2.8) and 128 (range: 104-165), respectively; P<0.01]. Furthermore, in patients with ovarian endometriosis, the levels of PT were significantly shorter in stage Ⅳ endometriosis than that in stage Ⅲ endometriosis (P<0.05). The levels of FIB and PLR in patients with stage Ⅳ endometriosis were significantly higher than those in patients with stage Ⅲ endometriosis (P<0.01) . (2) The cut-off value of CA(125) was 27.2 kU/L with a sensitivity of 83.6%, the cut-off value of FIB was 3.1 g/L with a sensitivity of 53.2%, while the sensitivity of combination index (FIB×CA(125)) was 84.9%. Conclusion: The abnormality of coagulation and inflammatory factors may be involved in the pathogenesis of moderate and severe ovarian endometriosis, and the detection of coagulation and inflammatory factors may be have important clinical significance for the diagnosis and treatment of moderate and severe ovarian endometriosis.
Climacteric. 2018 Apr 3:1-7.
Postmenopausal endometriosis: drawing a clearer clinical picture.
This review aims to draw a clearer clinical picture of postmenopausal endometriosis. Based on limited literature, postmenopausal endometriosis emerges as an infrequent entity but with a clinical picture significantly unlike that of premenopausal endometriosis. In contrast to the premenopausal disease, postmenopausal endometriosis occurs in a state of ovarian estrogen deficiency, appears to have a greater predisposition to malignant change, may have a greater tendency to spread to extragonadal organs and develop into constrictive and/or obstructive lesions, and is preferably treated surgically. The need to use hormone therapy for the management of menopausal symptoms that may concomitantly affect women with postmenopausal endometriosis is an unresolved therapeutic dilemma. This is mainly because the relationships of menopausal hormone therapy to recurrence of endometriosis and, more importantly, to increased risk of malignant degeneration, remain unclear.
Open Access Maced J Med Sci. 2018 Mar 5;6(3):519-522.
Acupuncture Treatment of Subfertility and Ovarian Endometrioma.
Ovarian endometriotic cysts, also known as ‘chocolate’ cysts or ovarian endometriomas, appear as endometrial tissue outside the uterine cavity which grows inside ovaries. Endometriotic cysts can cause chronic pelvic pain, dysmenorrhea, dyspareunia, impairment of ovarian function in regards to subfertility, etc. Traditional Chinese Medicine (TCM) is effectively treating subfertility associated with endometriosis for years, and the treatment gives positive results in achieving pregnancy. With the acupuncture treatment, blood circulation is promoted, external physical factors – eliminated, the stasis is dissolved, the menstrual cycle is regulated, and inflammation is diminished.
Our treated patient is 29-year-old woman diagnosed with ovarian endometrioma, slightly – elevated prolactin levels and inability to get pregnant after trying for two years. Ningteen acupuncture treatments were done on the meridians of Pericardium, Spleen, Stomach, Liver, Ren Mai, Kidney, Large intestine, Du Mai and Bladder. After the acupuncture treatments, the endometrioma was decreased in size and the patient got pregnant spontaneously in a short period.
Acupuncture, as part of the TCM, gives positive results and can successfully add up to variety of non – surgical infertility treatment options in women with endometrioma(s).
Zhonghua Nei Ke Za Zhi. 2018 Apr 1;57(4):275-278.
The colonoscopic characteristics of colorectal endometriosis: a single-centered retrospective study.
Objective: To reinforce the awareness of colorectal endometriosis (EM) in colonoscopy examination. Methods:Patients diagnosed as colorectal EM at Peking Union Medical College Hospital between February 2002 and February 2017 were enrolled in this study. The clinical characteristics and endoscopic features of EM lesions were summarized and compared between pathologically positive group and negative group. Results: A total of 34 cases were included with average age of (38.3±8.9) years old. All EM lesions located within rectum and sigmoid colon. The endoscopic lesions manifested as protrusion in 21 cases (61.8%) and protrusion-depression in 13 cases (38.2%), local stenosis in 8 cases (23.5%); erosive surface in 33 cases (97.1%) with local spontaneous hemorrhage in 4 cases (11.8%); nodal surface in 23 cases (67.6%), and lymphangiectasis base in 9 cases (26.4%). Endoscopic biopsy specimens were obtained in all cases with average 3 (2, 4) pieces. Positive results were found only in 4 patients (11.8%) with 3 endometriosis and one (endometrial) adenosarcoma. Compared with negative group, spontaneous hemorrhage was more frequent in positive group (2/4 vs. 2/30, P=0.013). Mean biopsy sample number was significantly larger in positive group (5 vs. 3, P=0.004). Conclusions: Colorectal endometriosis is mostly located within rectosigmoid region. Endoscopic features mainly include protrusion or protrusion-depression lesions with erosive and nodular surface, or local stenosis. Spontaneous hemorrhage under colonoscopy yields higher positive rate for biopsy, thus increasing biopsy sample numbers may improve pathology results.
J Transl Med. 2018 Apr 3;16(1):85.
An in vitro investigation of telocytes-educated macrophages: morphology, heterocellular junctions, apoptosis and invasion analysis.
Telocytes (TCs), a recently discovered novel type of interstitial cells, were also found in a wide variety of human and mammalian reproductive organs/tissues, including uterus, oviduct and placenta. Previously, we demonstrated that TCs-conditioned media was capable of activating peritoneal macrophages (pMACs) through paracrine effects. This study investigates the hypothesis that direct interaction of TCs with pMACs will also play a significant role in immunoregulation of pMACs.
TCs and pMACs were derived from the uterus and intraperitoneal cavity of female BALB/c mice, respectively. TCs were identified by immunofluorescence and then co-cultured directly with pMACs for 24 h without added cytokines, to observe the in vitro biological behavior of pMACs. We used histochemical staining to study morphology and mitochondrial metabolism of pMACs, scanning electron microscopy to study heterocellular junctions, flow cytometry to investigate mitochondrial membrane potential (ΔΨm) and apoptosis, and transwell chambers to study invasion ability. Student-t test was used accordingly.
Presently, TCs with typical structure and immunophenotype of double CD-34-positive/vimentin-positive were successfully isolated. pMACs co-cultured with TCs showed obviously morphological activation, with enhanced energy metabolism (P < 0.05). Meanwhile, direct physical cell-to-cell interaction promoted the development of heterocellular junctions between TCs and pMACs. Furthermore, TCs treatment markedly reduced the depletion of ΔΨm in co-cultured pMACs (all P < 0.05), and inhibited their apoptosis (P < 0.05). Functionally, pMACs co-cultured with TCs showed enhanced invasion ability (P < 0.05).
Direct physical cell-to-cell interaction promoted the development of heterocellular junctions between TCs and pMACs, presumably responsible for the observed novel efficient way of pMACs activation via mitochondrial signaling pathway. TCs-educated pMACs might be a promising way to restore the defective immunosurveillance in endometriosis (EMs), led to the enhanced treatment efficacy of EMs in a simple and clinically feasible fashion.
Reprod Biol Endocrinol. 2018 Apr 3;16(1):32..
Efficacy, safety and recurrence of new progestins and selective progesterone receptor modulator for the treatment of endometriosis: a comparison study in mice.
Current medical treatments for endometriosis are very limited. Progestin and selective progesterone receptor modulators (SPRM) are developed but their efficacy, safety, mechanism and recurrence in endometriosis are not fully studied.
In order to compare therapeutic, side effects and therapeutic actions of Esmya, Duphaston and Dienogest in endometriosis. Experimental endometriosis was induced by either intraperitoneal or subcutaneous mouse endometrium transplantation. Lesion size, weight and histology at the end of intervention were compared. Expression of related markers in the endometriotic lesions were examined. Body, uterus and ovary weights, endometrial glands and thickness (ETI), and follicle count were measured. For recurrent study, lesion growth before and after intervention was monitored.
After Esmya, Duphaston, Dienogest treatment, lesion size and weight were significantly decreased. Proliferation Pcna expression was significantly decreased in all groups, but proliferation cells were significantly decreased only in Duphaston group. Apoptosis Mapk1 expression and TUNEL-positive cells were significantly increased in Duphaston group. Adhesion Mmp2 and Itgavβ3 expression were significantly increased in Esmya group. Plau, Hif1α and Vegfa expression, peritoneal fluid PGE2 levels, and ERα and ERβ expression were not affected; while PR expression was significantly lower in all groups. Endometrial gland count in uterus was significantly increased in Dienogest group, ETI was significantly decreased in Duphaston group, and AFC were significantly increased in Esmya group. Upon treatment cessation, lesion growth rebound quickly in Dienogest and Duphaston groups, but slowly in Esmya group.
Esmya, Duphaston and Dienogest are effective anti-endometriosis drugs targeting proliferation, apoptosis and adhesion. Esmya, Duphaston and Dienogest are all well tolerable, although endometrial glandular hyperplasia was found in Dienogest, endometrial atrophy in Duphaston, follicle accumulation in Esmya.
Expert Opin Drug Metab Toxicol. 2018 Apr 10:1-17.
Current understanding on pharmacokinetics, clinical efficacy and safety of progestins for treating pain associated to endometriosis.
Endometriosis is a chronic estrogen and progestogen responsive inflammatory disease associated with pain symptoms and infertility. The medical therapy of endometriosis aims to induce decidualization within the hormonally dependent ectopic endometrium, and it is often administered to ameliorate women’ pain symptoms or to prevent post-surgical disease recurrence. A variety of progestins have been used in monotherapy for the medical management of women with endometriosis. Areas covered: This review aims to offer the reader a complete overview of pharmacokinetic (PK) and clinical efficacy of progestins for the treatment of endometriosis. Expert opinion: Each progestin has a distinct PK parameters and pharmacodynamics affinity not only for progesterone receptor, but also for other steroid receptors, such as estrogen, androgen, and glucocorticoid. Moreover, progestins can also be delivered in different formulations. All these characteristics influence their final biological effect. Randomized, controlled, non-blinded studies support the use of oral progestin-only treatment for pelvic pain associated with endometriosis. Currently, the only two progestins approved by Food and Drug Administration (FDA) for the treatment of endometriosis are norethindrone acetate (NETA) and depot medroxyprogesterone acetate (DMPA).
J Mol Endocrinol. 2018 Apr 4. pii: JME-18-0045.
Steroid Sulfatase Inhibition by Aryl Sulfamates: Clinical Progress, Mechanism and Future Prospects.
Steroid sulfatase is an emerging drug target for the endocrine therapy of hormone-dependent diseases, catalyzing estrogen sulfate hydrolysis to estrogen. Drug discovery, developing the core aryl O-sulfamate pharmacophore, has led to steroidal and non-steroidal drugs entering numerous clinical trials, with promising results in oncology and women’s health. Steroidal estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors and one was developed clinically as an oral estradiol pro-drug and for endometriosis applications. This review summarizes work leading to the therapeutic concept of sulfatase inhibition, clinical trials executed to date and new insights into the mechanism of inhibition of steroid sulfatase. To date the non-steroidal sulfatase inhibitor Irosustat has been evaluated clinically in breast cancer, alone and in combination, in endometrial cancer and in prostate cancer. The versatile core pharmacophore both imbues attractive pharmaceutical properties and functions via three distinct mechanisms of action, as a pro-drug, an enzyme active site-modifying motif, likely through direct sulfamoyl group transfer, and as a structural component augmenting activity, for example by enhancing interactions at the colchicine binding site of tubulin. Preliminary new structural data on the Pseudomonas aeruginosa arylsulfatase enzyme suggest two possible sulfamate-based adducts with active site hydrated formylglycine as candidates for the inhibition end product via sulfamoyl group transfer, and a speculative choice is suggested. The clinical status of sulfatase inhibition is surveyed and how it might develop in the future. Also discussed are dual-targeting approaches, development of 2-substituted steroidal sulfamates and nonsteroidal derivatives as multi-targeting agents for hormone-independent tumours with other emerging directions.