Endocrinology. 2009 Oct;150(10):4701-12. Epub 2009 Jul 9.Increased mitogen-activated protein kinase kinase/extracellularly regulated kinase activity in human endometrial stromal fibroblasts of women with endometriosis reduces 3',5'-cyclic adenosine 5'-monophosphate inhibition of cyclin D1.Velarde MC, Aghajanova L, Nezhat CR, Giudice LC.Department of Obstetrics, Center for Reproductive Sciences, University of California San Francisco, San ...
Int J Gynaecol Obstet. 2017 Nov 17.
Diagnostic accuracy of serum miR-122 and miR-199a in women with endometriosis.
To evaluate the value of serum microRNA-122 (miR-122) and miR-199a as reliable noninvasive biomarkers in the diagnosis of endometriosis.
During 2015-2016, at a teaching hospital in Egypt, a prospective cohort study was conducted on 45 women with pelvic endometriosis and 35 women who underwent laparoscopy for pelvic pain but were not diagnosed with endometriosis. Blood and peritoneal fluid (PF) samples were collected; interleukin-6 (IL-6) was detected by enzyme-linked immunosorbent assay and miR-122 and miR-199a expression was measured by quantitative real-time polymerase chain reaction.
The serum and PF levels of IL-6, miR-122, and miR-199a were significantly higher in women with endometriosis than in controls (P<0.001 for all comparisons). Serum miR-122 expression was positively correlated with serum IL-6 (r=0.597), PF IL-6 (r=0.603), PF miR-122 (r=0.934), serum miR-199a (r=0.727), and PF miR-199a (r=0.653). Serum miR-199a expression was positively correlated with serum IL-6 (r=0.677), PF IL-6 (r=0.678), PF miR-122 (r=0.744), and PF miR-199a (r=0.932). Serum miR-122 and miR-199a had a sensitivity of 95.6% and 100.0%, and a specificity of 91.4% and 100%, respectively, for the detection of endometriosis.
Serum miR-122 and miR-199a were significantly increased in endometriosis, indicating that these microRNAs might serve as biomarkers for the diagnosis of endometriosis.
Presse Med. 2017 Dec;46(12 Pt 1):1156-1165.
Pathogenesis, genetics and diagnosis of endometriosis.
Endometriosis is a multifactorial pathology. Trans-tubal reflux theory remains valid. Genetic and epigenetic factors associated with immunological perturbations are involved. The role of endocrine disruptors is discussed although epidemiological studies are contradictory. Therapeutics are primarily based on hormonal treatments but better understanding of pathophysiology should allow targeted non-hormonal therapy. The clinical examination is sometimes negative, which should not eliminate the diagnosis and imposes complementary examinations as best as possible by referents.
Clujul Med. 2017;90(4):411-415. doi: 10.15386/cjmed-743. Epub 2017 Oct 20.
Surgical scar endometriosis: a series of 14 patients and brief review of literature.
BACKGROUND AND AIMS:
Endometriosis is a commonly encountered disorder in women of reproductive age, consisting of the presence of active ectopic endometrial tissue outside the endometrial cavity. Surgical scar endometriosis is a rare condition representing about 2% of all endometriosis cases. The purpose of this study was to assess the main characteristics, diagnostic tools and therapeutic options in abdominal wall endometriosis (AWE).
We have reviewed a series of fourteen cases with histopathological confirmation of AWE that were managed in our institution.
The main characteristic of AWE were emphasized, showing that 78.57% of the patients had at least one previous caesarian section and that in only 57.14% of all cases an accurate diagnosis of AWE was established preoperatively.
A direct relationship between gynecological and obstetrical surgery and AWE is well established and as the caesarian section rates increase constantly, the awareness regarding AWE should also be increased.
Presse Med. 2017 Dec;46(12 Pt 1):1166-1172.
Imaging in the initial and preoperative assessment of endometriosis.
The diagnosis of pelvic endometriosis is based on the combination of clinical examination, endovaginal ultrasonography and pelvic MRI. Ultrasonography displays a moderate sensitivity and a high specificity. Pelvien MRI displays a better sensitivity and lower specificity.
J Reprod Immunol. 2017 Oct 27;125:1-7.
The endometria of women with endometriosis exhibit dysfunctional expression of complement regulatory proteins during the mid secretory phase.
The control of complement activation within embryo-endometrium environment is critical for embryo survival. Cell evasion from complement attack requires interaction of complement regulatory proteins (CRPs) with cell adhesion αvβ3 integrin. We aim to compare the expression of CRPs in endometria of women with and without endometriosis and to examine the molecular interaction of decay accelerating factor (DAF) with αvβ3 integrin. Endometrial expression of Membrane cofactor protein (CD46), Decay accelerating factor (DAF), Membrane attack complex inhibitory factor (CD59) and β3 integrin subunit were determined through menstrual cycle by immunohistochemistry. DAF protein quantity was determined by Western blot and mRNA levels measured in epithelial cells isolated by laser capture microdissection (LCM). Using in vitro assay, we examined DAF and β3 integrin expression through paracrine regulation between endometrial compartments. To determine whether β3 integrin and DAF interacts in vivo, endometrial samples were subjected to immunoprecipitation and colocalization using dual immunofluorescence technique. DAF and β3 integrin expression were significantly low in samples from women with endometriosis during mid secretory phase. This observation was supported by decreased DAF protein quantity; faint DAF and β3 integrin interaction and reduced mRNA levels in cells dissected by LCM. Moreover epithelial DAF and β3 integrin expression through paracrine regulation by progesterone from stromal compartment was disrupted in endometriosis. Endometria from women with endometriosisexhibits aberrant expression of complement proteins. The abnormal DAF expression potentially compromises embryo survival, contributing to understand the implantation failure in women with endometriosis.
Ultrasound Obstet Gynecol. 2017 Nov 20.
Transvaginal ultrasound (TVS) versus Magnetic Resonance (MR) for diagnosing deep infiltrating endometriosis: a systematic review and meta-analysis.
To perform a systematic review of studies comparing the diagnostic accuracy of TVS and MRI in Deep Infiltrating Endometriosis (DIE) including only studies in which patients have been underwent both techniques.
An extensive search of papers comparing TVS and MRI in DIE was performed in Medline (Pubmed) and Web of Sciences from January 1989 to January 2016. Studies were considered eligible if they reported on the use of TVS and MRI in the same set of patients for the preoperative detection of endometriosis in pelvic locations in women with clinical suspicion of DIE using the surgical data as a reference standard. Quality was assessed using QUADAS-2 tool. A random-effects model was used to determine overall pooled sensitivity, specificity, positive likelihood ratio (LR+) and negative likelihood ratio (LR-) and the diagnostic odds ratio (DOR).
Of the 375 citations identified, 6 studies (n=424) were considered eligible. Pooled sensitivity, specificity, LR+ and LR- of MRI in detecting DIE in the recto-sigmoid for MRI were 0.85 (95% CI, 0.78-0.90), 0.95 (95% CI, 0.83-0.99), 18.4 (95% CI, 4.7-72.4) and 0.16 (95% CI, 0.11-0.24), respectively. Pooled sensitivity, specificity, LR+ and LR- of TVS in detecting DIE in the recto-sigmoid for TVS were 0.85 (95% CI, 0.68-0.94), 0.96 (95% CI, 0.85-0.99), 20.4 (95% CI, 4.7-88.5) and 0.16 (95% CI, 0.07-0.38), respectively. DOR was 116 (95% CI, 23-585) and 127 (95% CI, 14 – 1126), respectively. Pooled sensitivity, specificity, LR+ and LR- of MRI in detecting DIE in the rectovaginal septum for MRI were 0.66 (95% CI, 0.51-0.79), 0.97 (95% CI, 0.89-0.99), 22.5 (95% CI, 6.7-76.2) and 0.38 (95% CI, 0.23-0.52), respectively. Pooled sensitivity, specificity, LR+ and LR- of TVS in detecting DIE in the rectovaginal septum for TVS were 0.59 (95% CI, 0.26-0.86), 0.97 (95% CI, 0.94-0.99), 23.5 (95% CI, 9.1-60.5) and 0.42 (95% CI, 0.18-0.97), respectively. DOR was 65 (95% CI, 21- 204) and 56 (95% CI, 11 – 275), respectively. Pooled sensitivity, specificity, LR+ and LR- of MRI in detecting DIE in the uterosacral ligaments for MRI were 0.70 (95% CI, 0.55-0.82), 0.93 (95% CI, 0.87-0.97), 10.4 (95% CI, 5.1-21.2) and 0.32 (95% CI, 0.20-0.51), respectively. Pooled sensitivity, specificity, LR+ and LR- of TVS in detecting DIE in the uterosacral ligaments for TVS were 0.67 (95% CI, 0.55-0.77), 0.86 (95% CI, 0.73-0.93), 4.8 (95% CI, 2.6-9.0) and 0.38 (95% CI, 0.29-0.50), respectively. DOR was 32 (95% CI, 12- 85) and 12 (95% CI, 7- 24), respectively. Wide confidence intervals of pooled sensitivities, specificities and DOR were present for both techniques in all the considered locations. Heterogeneity was moderate or high for sensitivity and specificity for TVS and MRI in most locations assessed. According to QUADAS2, the quality of the studies was considered good for most domains of the included studies.
Overall diagnostic performance of TVS and MRI for detecting DIE involving recto-sigmoid, uterosacral ligaments and rectovaginal septum is similar.
Reprod Sci. 2017 Jan 1:1933719117741372.
Trichostatin A Induces NAG-1 Expression and Apoptosis in Human Endometriotic Stromal Cells.
To investigate the effects of trichostatin A (TSA) on nonsteroidal anti-inflammatory drug-activated gene 1 (NAG-1) expression and apoptosis in human endometriotic stromal cells (HESCs), ectopic endometrial tissues were obtained from 15 patients with endometriotic cysts who underwent cystectomy. Human endometriotic stromal cells were isolated and cultured with different concentrations of TSA. Nonsteroidal anti-inflammatory drug-activated gene-1 messenger RNA (mRNA) and protein levels were evaluated by real-time polymerase chain reaction and Western blotting, respectively, and apoptosis was assessed by flow cytometry. Viability of HESCs was reduced in a dose-dependent manner by treatment with TSA. The percentage of early and late apoptotic HESCs was increased upon treatment with TSA. Nonsteroidal anti-inflammatory drug-activated gene-1 mRNA and protein expression was induced in a dose-dependent manner by TSA treatment. Gene knockdown experiments using small-interfering RNA confirmed an association between NAG-1 expression and TSA-induced apoptosis. Whether effects of TSA on NAG-1 gene expression are enhanced in the presence of 5-aza-2′-deoxycytidine (5-aza-dC) are also investigated; however, TSA-induced apoptosis was unaffected by 5-aza-dC. In conclusion, TSA induced apoptosis in HESCs via induction of NAG-1 expression. These results suggest that upregulation of NAG-1 contributes to TSA-induced apoptosis in HESCs.
J Minim Invasive Gynecol. 2017 Nov 20.
Magnetic Resonance Enterography to Assess Multifocal and Multicentric Bowel Endometriosis.
To prospectively determine the accuracy of magnetic resonance enterography (MRE) compared with conventional magnetic resonance imaging (MRI) for multifocal (i.e., multiple lesions affecting the same digestive segment) and multicentric (i.e., multiple lesions affecting several digestive segments) bowel endometriosis.
A prospective study (Canadian Task Force classification II-2).
Tenon University Hospital, Paris, France.
Patients with MRI-suspected colorectal endometriosis scheduled for colorectal resection from April 2014 to February 2016 were included.
Patients underwent both 1.5-Tesla MRI and MRE as well as laparoscopically assisted and open colorectal resections.
MEASUREMENTS AND MAIN RESULTS:
The diagnostic performance of MRI and MRE was evaluated for sensitivity, specificity, positive and negative predictive values, accuracy, and positive and negative likelihood ratios (LRs). The interobserver variability of the experienced and junior radiologists was quantified using weighted statistics. Forty-seven patients were included. Twenty-two (46.8%) patients had unifocal lesions, 14 (30%) had multifocal lesions, and 11 (23.4%) had multicentric lesions. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multifocal lesions were 0.29 (6/21), 1.00 (23/24), 15.36, and 0.71 for MRI and 0.57 (12/21), 0.89 (23/25), 4.95, and 0.58 for MRE. The sensitivity, specificity, positive LR, and negative LR for the diagnosis of multicentric lesions were 0.18 (1/11), 1.00 (1/1), 15, and 0.80 for MRI and 0.46 (5/11), 0.92 (33/36), 5.45, and 0.60 for MRE. Lower accuracies for MRI compared with MRE to diagnose multicentric (p = .01) and multifocal lesions (p = .004) were noted. The interobserver agreement for MRE was good for both multifocality (κ = 0.80) and multicentricity (κ = 0.61).
MRE has better accuracy for diagnosing multifocal and multicentric bowel endometriosisthan conventional MRI.
Gynecol Endocrinol. 2017 Nov 21:1-5.
Short-term histopathological effects of dienogest therapy on ovarian endometriomas: in vivo, nonrandomized, controlled trial.
Ovarian endometriosis is a common gynecological disorder. To date, progestins are recommended as the first-line medical treatment for symptomatic ovarian endometriosis. The aim of this study was to evaluate the main histopathological effects of short-term dienogest therapy in patients with ovarian endometriomas scheduled for surgery. A prospective, nonrandomized controlled trial, including 70 symptomatic women with single ovarian endometriotic cyst (diameter between 30-50 mm) was conducted. Women scheduled for surgery were divided into two groups, depending on the treatment established at enrollment: 36 women received progestin therapy with dienogest (P group) and 34 women received no therapy (C group). At histopathological examination necrosis, inflammation, decidualization, glandular atrophy and angiogenesis were blindly evaluated. At tissue level, decidualization was significantly more frequent in P group compared to C group (p = .001). A nonsignificant tendency (p = .29) towards a slight decreased inflammation in P group was found. No significant differences were observed between the two groups in terms of necrosis, glandular atrophy and angiogenesis. The study suggests that high decidualization rate and the tendency to reduced inflammatory reaction in the short-term administration of dienogest might contribute to its therapeutic efficacy.
Biol Reprod. 2017 Nov 17.
Pharmacological blockage of the CXCR4-CXCL12 axis in endometriosisleads to contrasting effects in proliferation, migration and invasion.
High levels of inflammatory factors including chemokines have been reported in peritoneal fluid and blood of women with endometriosis. CXCL12 mediates its action by interaction with its specific receptor, CXCR4, which has been reported to be elevated in human endometriosis lesions and in the rat model of endometriosis. Activation of the CXCR4-CXCL12 axis increases cell proliferation, migration and invasion of cancer cells. To obtain insights into the CXCR4 expression profile in lesions and endometrium, as well as functionality of the CXCR4-CXCL12 axis in endometriosis we analysed the expression of CXCR4 in tissues on a human tissue array and studied CXCL12-mediated activation of proliferation, invasion, and migration in vitro. We observed differences in levels of nuclear CXCR4 expression among lesion types, being higher in ovarian lesions. Endometriotic cell lines (12Z) showed higher levels of CXCR4, proliferative and migratory potential, and AKT phosphorylation/kinase activity compared to untreated control cells (EEC). CXCL12 and endometriotic stromal cell-enriched media increased proliferation of non-endometriotic epithelial cells. CXCL12 caused a significant increase in 12Z cell invasion but had no effect on migration; AMD3100, a CXCR4-specific inhibitor, significantly increased invasion of 12Z cells but decreased their migration. However, treatment with CXCL12 plus AMD3100 significantly decreased invasion and migration of 12Z cells. In conclusion, the CXCR4-CXCL12 axis is functional in endometriosis cells, but the expression of CXCR4 varies among lesions. CXCL12 promoted proliferation, migration, and invasion of endometriotic cells, while inducing AKT phosphorylation and activity, but pharmacologically blocking this axis in the absence of the ligand induced their invasiness.
Reprod Sci. 2017 Jan 1:1933719117725820.
Efficacy and Safety of Long-Term Use of Dienogest in Women With Ovarian Endometrioma.
Dienogest (DNG) is a progestin with highly selective progesterone activity and minimal androgenic activity and is helpful in reducing endometriosis-related pain. This study assessed the long-term efficacy and safety and recurrence rate of endometrioma with DNG use beyond 12 months of treatment. A retrospective cohort study was conducted with data collected from 7 university-affiliated hospitals and included a total of 514 women with ovarian endometrioma. All patients received 2 mg of oral DNG daily for at least 48 weeks postoperatively. During continuation of DNG, the recurrence rate of ovarian endometrioma on ultrasound, adverse events, changes in menstrual pattern, and pain score (visual analogue scale) were analyzed. The average period of DNG administration in this study was 72.2 ± 5.2 weeks (range: 48-164). The recurrence rate of endometrioma was 1.8% (9 of 514), and the median duration to recurrence was 58 weeks (range: 24-76). Pain was described as overall improved by 82.2% of patients; 61.6% stated the pain was “improved” and 20.6% reported “much improved.” The mean VAS score was 4.9 at baseline and significantly decreased to 2.68, 2.2, 1.6, and 2.6 at 12, 24, 48, and 96 weeks. Amenorrhea rate was 58.3% in the first 12 weeks and increased to 86.4% at 72 weeks. Prolonged daily administration of 2 mg DNG followed by surgery was associated with a lower recurrence rate of ovarian endometrioma and a reduced pain score and symptoms.
BMC Surg. 2017 Nov 21;17(1):107.
Martius’ flap for recurrent perineal and rectovaginal fistulae in a patient with Crohn’s disease, endometriosis and a mullerian anomaly.
Rectovaginal fistulas represent 5% of all anorectal fistulae and are a disastrous manifestation of Crohn’s disease that negatively affects patients’ social and sexual quality of life. Treatment remains challenging for colorectal surgeons, and the recurrence rate remains high despite the numerous available options.
We describe a 31-year-old female patient with a Crohn’s disease-related recurrent perineo-vaginal and recto-vaginal fistulae and a concomitant mullerian anomaly. She complained of severe dyspareunia associated with penetration difficulties. The patient’s medical history was also significant for a previous abdominal laparoscopic surgery for endometriosis for the removal of macroscopic nodules and a septate uterus with cervical duplication and a longitudinal vaginal septum. The patient was successfully treated using a Martius’ flap. The postoperative outcome was uneventful, and no recurrence of the fistula occurred at the last follow-up, eight months from the closure of the ileostomy.
Martius’ flap was first described in 1928, and it is considered a good option in cases of rectovaginal fistulas in patients with Crohn’s disease. The patient should be referred to a colorectal centre with expertise in this disease to increase the surgical success rate.
Cold Spring Harb Mol Case Stud. 2017 Nov 21;3(6).
Elucidating the pathogenesis of synchronous and metachronous tumors in a woman with endometrioid carcinomas using a whole-exome sequencing approach.
Synchronous endometrial and ovarian (SEO) carcinomas involve endometrioid neoplasms in both the ovary and uterus at the time of diagnosis. Patients were traditionally classified as having independent primary SEO lesions or as having metastatic endometrioid carcinoma. Recent studies have supported that SEO tumors result from the dissemination of cells from one organ site to another. However, whether this can be considered a “metastasis” or “dissemination” remains unclear. In this report, we performed whole-exome sequencing of tumor samples from a woman with well-differentiated endometrioid SEO tumors and a clinical “recurrent” poorly differentiated peritoneal tumor that was diagnosed 8 years after the complete resection of the SEO tumors. Somatic mutation analysis identified 132, 171, and 1214 nonsynonymous mutations in the endometrial, ovarian, and peritoneal carcinomas, respectively. A unique mutation signature associated with mismatch repair deficiency was observed in all three tumors. The SEO carcinomas shared 57 nonsynonymous mutations, whereas the clinically suspected recurrent carcinoma shared only eight nonsynonymous mutations with the SEO tumors. One of the eight shared somatic mutations involved PTEN; these shared mutations represent the earliest genetic alteration in the ancestor cell clone. Based on analysis of the phylogenetic tree, we predicted that the so-called recurrent peritoneal tumor was derived from the same endometrial ancestor clone as the SEO tumors, and that this clone migrated and established benign peritoneal endometriosis where the peritoneal tumor later arose. This case highlights the usefulness of next-generation sequencing in defining the etiology and clonal relationships of synchronous and metachronous tumors from patients, thus providing valuable insight to aid in the clinical management of rare or ambiguous tumors.
J Obstet Gynaecol India. 2017 Dec;67(6):385-392.
Intrauterine Insemination: Fundamentals Revisited.
Intrauterine insemination (IUI) is an assisted conception technique that involves the deposition of a processed semen sample in the upper uterine cavity, overcoming natural barriers to sperm ascent in the female reproductive tract. It is a cost-effective, noninvasive first-line therapy for selected patients with functionally normal tubes, and infertility due to a cervical factor, anovulation, moderate male factor, unexplained factors, immunological factor, and ejaculatory disorders with clinical pregnancy rates per cycle ranging from 10 to 20%. It, however, has limited use in patients with endometriosis, severe male factor infertility, tubal factor infertility, and advanced maternal age ≥ 35 years. IUI may be performed with or without ovarian stimulation. Controlled ovarian stimulation, particularly with low-dose gonadotropins, with IUI offers significant benefit in terms of pregnancy outcomes compared with natural cycle or timed intercourse, while reducing associated COH complications such as multiple pregnancies and ovarian hyperstimulation syndrome. Important prognostic indicators of success with IUI include age of patient, duration of infertility, stimulation protocol, infertility etiology, number of cycles, timing of insemination, number of preovulatory follicles on the day of hCG, processed total motile sperm > 10 million, and insemination count > 1 × 106 with > 4% normal spermatozoa. Alternative insemination techniques, such as Fallopian tube sperm perfusion, intracervical insemination, and intratubal insemination, provide no additional benefit compared to IUI. A complete couple workup that includes patient history, physical examination, and clinical and laboratory investigations is mandatory to justify the choice in favor of IUI and guide alternative patient management, while individualizing the treatment protocol according to the patient characteristics with a strict cancelation policy to limit multi-follicular development may help optimize IUI pregnancy outcomes.
Hawaii J Med Public Health. 2017 Nov;76(11 Suppl 2):7-9.
Spontaneous Endometriosis Within a Primary Umbilical Hernia.
Umbilical hernias are rather common in the General Surgery clinic; however, endometriosis of an umbilical hernia is rare. It is especially unusual to have endometriosis of an umbilical hernia spontaneously occur compared to occurring at a site of a prior surgery. We present a case of spontaneous endometriosis of an umbilical hernia without prior surgery to her umbilicus. She had not presented with the usual symptoms of endometriosis and it was not considered as a diagnosis prior to surgery. Umbilical endometriosis is rare but usually occurs after prior laparoscopic surgery. We believe this is the second reported case in the English literature and the first such case reported from North America of spontaneous endometriosis of an umbilical hernia. This case highlights the importance of a full review of systems and qualifying the type and occurrence of pain. Additionally, it is always important to analyze surgical specimens in pathology to avoid errors in diagnosis.
Climacteric. 2018 Feb;21(1):88-91.
Endometriosis resembling endometrial cancer in a postmenopausal patient.
Endometriosis occurs in 2-4% of postmenopausal women. There have been a few reports of endometriosisin women in whom neither history nor diagnostic imaging indicated the presence of this disease, either at reproductive age or after menopause. A case is described of an 84-year-old patient with extensive deep pelvic endometriosis imitating advanced neoplastic process.
Endocrinology. 2018 Jan 1;159(1):477-489.
Epigenetic Therapy: Novel Translational Implications for Arrest of Environmental Dioxin-Induced Disease in Females.
Increased toxicant exposure and resultant environmentally induced diseases are a tradeoff of industrial productivity. Dioxin [2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD)], a ubiquitous byproduct, is associated with a spectrum of diseases including endometriosis, a common, chronic disease in women. TCDD activates cytochrome (CYP) p450 metabolic enzymes that alter organ function to cause disease. In contrast, the transcription factor, Krüppel-like factor (KLF) 11, represses these enzymes via epigenetic mechanisms. In this study, we characterized these opposing mechanisms in vitro and in vivo as well as determining potential translational implications of epigenetic inhibitor therapy. KLF11 antagonized TCDD-mediated activation of CYP3A4 gene expression and function in endometrial cells. The repression was pharmacologically replicated by selective use of an epigenetic histone acetyltransferase inhibitor (HATI). We further showed phenotypic relevance of this mechanism using an animal model for endometriosis. Fibrotic extent in TCDD-exposed wild-type animals was similar to that previously observed in Klf11-/- animals. When TCDD-exposed animals were treated with a HATI, Cyp3 messenger RNA levels and protein expression decreased along with disease progression. Fibrotic progression is ubiquitous in environmentally induced chronic, untreatable diseases; this report shows that relentless disease progression can be arrested through targeted epigenetic modulation of protective mechanisms.
Aust N Z J Obstet Gynaecol. 2017 Nov 23
Pelvic examination may be meaningfully taught to novices and be used to predict operating times for laparoscopic excision of endometriosis in one surgical procedure.
To investigate whether pelvic examination may be meaningfully taught to novice medical students and its accuracy in predicting operating times for laparoscopic excision of endometriosis at a single surgical procedure.
Women with suspected endometriosis scheduled for laparoscopy underwent pelvic examination to estimate operative time by medical students (novices), trainees, senior clinicians with <10 years surgical experience (experts) and ≥10 years (masters). Examination and intraoperative findings were compared and stage of disease recorded.
There were 138 estimations of operating time at the initial assessment and 251 estimations of operating time prior to surgery. The median surgical duration was 44 min (range 12-398) and increased progressively with revised American Society for Reproductive Medicine disease stage. Clinical predictions exceeded actual operating times by a median of 18 min (range overestimating by 180 min and underestimating by 120 min) with 80% of procedures completed in less time than predicted and none requiring a second procedure. There was no statistical difference in operative time estimations between the groups with students and trainees underestimating surgical duration by a median of two and five minutes, respectively, experts having a median time difference of zero minutes, and masters overestimating by 4.5 min.
Targeted pelvic examining may be taught to novices (medical students) and can be used to predict operating time at one surgical procedure. Less experienced examiners have a tendency to underestimate surgical duration, with masters overestimating surgical time when scheduling laparoscopies for endometriosis, and increasing disease stage is associated with a less precise estimation of surgical duration.
Presse Med. 2017 Dec;46(12 Pt 1):1218-1222.
Creation of expert centers on endometriosis.
Endometriosis is a frequent pathology with a high incidence of deep infiltrating endometriosis and complex forms that can affect 20% of patients with endometriosis. The incidence of infertility associated with endometriosis can reach 50%. The complexity of care requires the creation of expert centers working in networks with general practitioners. Criteria for defining these expert centers are being drawn up, based on structural criteria (multidisciplinary consultation meeting), links with medical assistance structures for procreation and activity criteria for severe and complex forms (number of interventions per center and per surgeon).
Prog Urol. 2018 Jan;28(1):2-11.
Detrusor sphincter disorders associated with deep endometriosis: Systematic review of the literature.
Detrusor sphincter disorders impact quality of life in case of deep endometriosis. Surgery, which is one of the main treatments, is responsible of detrusor sphincter disorders. Since then, it is essential to look for those disorders and find the right medical care.
To specify the detrusor sphincter disorders, its links with anatomical localisation of deep endometriosis and its prognosis after surgery.
A literature review was carried out via PubMed® with the followings keywords: “deep endometriosis”, “urinary disorders”, “voiding dysfunction” and “urinary dysfunction”. Prospective and retrospective studies as well as previous reviews were analyzed.
Concerning bladder deep endometriosis, detrusor sphincter disorders are observed in more than 50%. Resection of the lesions allows a clear improvement or even a disappearance of the disorders. Concerning the deep endometriosis of the posterior part of the pelvis, disorders are highlighted even if women do not complain of urinary trouble. Detrusor sphincter disorders are observed in 2 to 50% and women with colorectal localisation have the highest rate. Resection of the lesions improves the symptoms described preoperatively but also provides de novo disorders of up to 47.5%. In terms of prevention, the nerve sparing surgery respects the pelvic nerve plexus, and reduces post-operative morbidity to less than 1%.
Detrusor sphincter disorders associated with deep endometriosis have a prognosis if their management is adapted. Well-conducted interviews and standardized questionnaires is necessary to diagnosis them. Urodynamic test may be discussed in case of bladder endometriosis, including for urinary asymptomatic patients. The management of the detrusor sphincter disorders requires a complete resection of the nodules of deep endometriosis. In the case of posterior endometriosis, a dissection must be performed respecting the retroperitoneal vegetative nerves.
Anim Reprod Sci. 2018 Jan;188:51-56.
Platelets are involved in in vitro swine granulosa cell luteinization and angiogenesis.
During corpus luteum formation, impressive biological events take place to guarantee the transition from original follicular to luteal cells and to support required massive angiogenesis. It has been demonstrated that these phenomena resemble those essential for wound healing. After ovulation, blood vessels release their content in the antral cavity and coagulation takes place. Involvement of platelets in corpus luteum growth has been hypothesized both in human and in rat. On this basis, using platelet lysate (PL), a blood derivative with a higher platelet concentration, we aimed to assess a potential involvement of platelets in swine granulosa cell luteinization and on new blood vessel growth. Our results demonstrate, for the first time in the swine, that platelets could be directly involved in granulosa cell physiological luteinization, since the treatment with PL shifted steroid production from estradiol 17β to progesterone. Moreover, PL stimulated angiogenesis. Nitric oxide could be involved in these effects. These results are important to clarify complex intrafollicular molecular machinery. A better understanding of these mechanisms can be useful to develop more focused therapeutic strategies to contrast sow infertility. In addition, since the pig represents a model for translational studies, collected data could be of interest for human medicine because reproductive pathologies such as Polycystic Ovary Syndrome (PCOS) and endometriosis are often accompanied by platelet dysfunctions.
Reprod Biomed Online. 2018 Jan;36(1):102-114.
Progress in the diagnosis and management of adolescent endometriosis: an opinion.
Increasing evidence indicates that early onset endometriosis (EOE), starting around menarche or early adolescence, may have an origin different from the adult variant, originating from neonatal uterine bleeding (NUB). This implies seeding of naïve endometrial progenitor cells into the pelvic cavity with NUB; these can then activate around thelarche. It has its own pathophysiology, symptomatology and risk factors, warranting critical management re-evaluation. It can also be progressive, endangering future reproductive capacity. This variant seems to be characterized by the presence of ovarian endometrioma. Today, the diagnosis of endometriosis in young patients is often delayed for years; if rapidly progressive, it can severely affect pelvic organs, even in the absence of serious symptoms. Given the predicament, great attention must be paid to symptomatology that is often non-specific, justifying a search for new, simple, non-invasive markers of increased risk. Better use of modern imaging techniques will aid considerably in screening for the presence of EOE. Traditional laparoscopy should be limited to cases in which imaging gives rise to suspicion of severity and a stepwise, minimally invasive approach should be used, followed by medical treatment to prevent recurrence. In conclusion, EOE represents a condition necessitating early diagnosis and stepwise management, including medical treatment.
Presse Med. 2017 Dec;46(12 Pt 1):1173-1183.
Management of endometrioma.
Preoperative evaluation: clinical examination, and research for associated lesions. Laparoscopic approach. Cystectomy: gold standard, conformed to the endometrioma pathophysiology (3 zones). Laser CO2Plasmajet® vaporisation: important data lead to legitimate utilisation. Haemostasis: be patient! Use of bipolar energy sparingly. Look for other endometriotic lesions, and systematic treatment. Preoperative medical treatment not always useful. Postoperative treatment: decrease recurrence. Especially for patients with no immediate pregnancy desire.
Int J Gynaecol Obstet. 2017 Nov 24.
Tuboperitoneal anomalies among infertile women in Nigeria as seen on laparoscopy.
To study the prevalence and pattern of tuboperitoneal pathologies among infertile women in Nigeria, using laparoscopy.
A prospective study was undertaken of infertile women who underwent diagnostic laparoscopy in two fertility clinics in Nigeria between November 2015 and April 2017. The rates of identified tuboperitoneal diseases were examined.
The age of the 230 women ranged from 21 to 46 years, and most women had a parity group of 0-1 (87.8%; n=202). Secondary infertility accounted for 124 (53.9%) cases, and the mean duration of infertility was 4.6 ± 2.7 years. Tuboperitoneal pathologies were seen in 171 (74.4%) women and mainly comprised tubal occlusion (56.5%; n=130), hydrosalpinx (41.7%; n=96), pelvic adhesions (39.6%, n=91), and endometriosis (8.8%; n=19). Bilateral tubal occlusion was seen in 46 (20.0%) women, whereas proximal tubal occlusion accounted for 73 (56.2%) of all cases of tubal occlusion.
There was a high rate of tuboperitoneal abnormalities in the studied population, which mainly comprised tubal occlusion, hydrosalpinx, pelvic adhesions, and endometriosis. The introduction of laparoscopy is recommended in the initial evaluation of all women with infertility in Nigeria.
J Pathol. 2018 Feb;244(2):131-134.
Origin of clear cell carcinoma: nature or nurture?
A rare but serious complication of endometriosis is the development of carcinoma, and clear cell and endometrioid carcinomas of the ovary are the two most common malignancies which arise from endometriosis. They are distinct diseases, characterized by unique morphologies, immunohistochemical profiles, and responses to treatment. However, both arise in endometriosis and can share common mutations. The overlapping mutational profiles of clear cell and endometrioid carcinomas suggest that their varied histologies may be due to a different cell of origin which gives rise to each type of cancer. Cochrane and colleagues address this question in a recent article in this journal. They show that a marker of ovarian clear cell carcinoma, cystathionine gamma lyase, is expressed in ciliated cells. Similarly, they show that markers of secretory cells (estrogen receptor and methylenetetrahydrofolate dehydrogenase 1) are expressed in ovarian endometrioid carcinoma. Taken together, they suggest that endometrioid and clear cell carcinomas arise from cells related to secretory and ciliated cells, respectively. We discuss Cochrane et al’s work in the context of other efforts to determine the cell of origin of gynecological malignancies, with an emphasis on recent developments and challenges unique to the area. These limitations complicate our interpretation of tumor differentiation; does it reflect nature imposed by a specific cell of origin or nurture, by either mutation(s) or environment? Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Biomed J. 2017 Oct;40(5):241-244.
Oxidative stress and diabetes: Glucose response in the cROSsfire.
In this issue of the Biomedical Journal, we discuss the emerging role of reactive oxygen species (ROS) in the development of insulin resistance and ultimately type 2 diabetes. We focus also on research investigating the outcome of in vitro fertilization after laproscopic surgery for ovarian endometriosis. Finally, we learn the results of a study on the hunt for new probiotic bacteria.
Int J Nanomedicine. 2017 Nov 9;12:8171-8183.
Effect of A-317491 delivered by glycolipid-like polymer micelles on endometriosis pain.
Endometriosis is a common gynecological disease with a lack of effective clinical treatment. Current therapy often results in endometriosis pain recurrence and serious side effects. P2X3 receptor, an adenosine triphosphate (ATP)-gated ion channel, might be implicated in endometriosis pain. In this study, chitosan oligosaccharide-g-stearic acid (CSOSA) polymer micelles-coated nanostructured lipid carriers (NLCs) were developed as a novel delivery system for A-317491, a selective P2X3 receptor antagonist for endometriosis pain therapy. A-317491-loaded NLC (NLC/A-317491) could be coated by CSOSA micelles to form CSOSA/NLC/A-317491 nanoparticles. Pheochromocytoma PC12 cells, which highly expressed P2X3receptors, were used as a cell model, and the CSOSA/NLC/A-317491 partly blocked the Ca2+ influx induced by ATP stimulation. In nude mouse and rat endometriotic models, CSOSA/NLC could accumulate into endometriotic lesions after vein injection. In endometriotic rats, CSOSA/NLC/A-317491 reversed mechanical and heat hyperalgesia with long-term efficacy, which might be attributed to the massive CSOSA/NLC/A-317491 distribution in the endometriotic lesions. In conclusion, A-317491 delivered by CSOSA/NLC nanoparticles attenuated endometriosis pain in rats, and CSOSA/NLC/A-317491 could be used as an effective treatment strategy for P2X3-targeted therapy in endometriosis pain.
Obstet Gynecol Sci. 2017 Nov;60(6):579-586.
Comorbidity of gynecological and non-gynecological diseases with adenomyosis and endometriosis.
Adenomyosis and endometriosis are relatively common gynecological diseases that exhibit many common features. This study identified gynecological and non-gynecological diseases that exhibited comorbidity with adenomyosis and endometriosis in Korean women.
We used Health Insurance Review and Assessment data from 2009 to 2011 and searched for adenomyosis and endometriosis (coded as N80.1 and D25 in International Classification of Disease, 10th revision [ICD-10], respectively). We selected records from patients who had independent disease occurrences in each year, and comorbidities were estimated using Fisher’s exact test. We computed each year’s similarities and combined 3 years’ results using Fisher’s P-value summation method.
A total of 61,516 patients’ data were collected during the study period. The prevalence of adenomyosis and endometriosis were similar each year: 12.4% and 9.3% in 2009, 12.5% and 9.4% in 2010 and 13.3% and 9.1% in 2011, respectively. Meta-analysis revealed that 31 ICD-10 codes were significantly related with adenomyosis, and 44 ICD-10 codes were related with endometriosis. Gynecological diseases, such as leiomyoma and benign ovarian tumor, were significantly related to adenomyosis and endometriosis. Non-gynecological diseases, such as anemia and hypercholesterolemia, were also related to adenomyosis and endometriosis.
We must monitor for the presence of gynecological and non-gynecological diseases with co-morbidities during evaluations and follow-up of patients with adenomyosis or endometriosis.
Surg J (N Y). 2017 Nov 27;3(4):e167-e173.
Laparoscopic Ureteral Reimplantation in Endometriosis: A Severe Case.
In aggressive cases, endometriosis can perturb the urogenital tract, in particular the ureter, which can potentially result in ureteral compression or stenosis. Even though this is rare, consequences are dramatic, such as hydronephrosis or organ failure. The present standard intervention comprises the resection of affected tissues and endometriosis foci combined with adjuvant hormonal therapy. When the ureter does not recover, ureteral reimplantation is required. The present case describes the successful laparoscopic approach of the reimplantation of the ureter with simultaneous cystoscopy.
Reprod Biomed Online. 2018 Feb;36(2):197-205.
The association between experiences with patient-centred care and health-related quality of life in women with endometriosis.
In this cross-sectional study, we investigated whether patient-centred endometriosis care (PCEC) is associated with health-related quality of life (HRQOL). Dutch-speaking women with endometriosis, treated by laparoscopy in a university clinic between 2009 and 2010, were eligible (n = 194). Endometriosis Health Profile-30 and ENDOCARE questionnaire were used to assess HRQOL and PCEC, respectively. Overall and subscale scores were converted to a scale from 0 (best score) to 100 (worst score). Linear regression analyses were conducted while controlling for confounders. Participants (n = 109) had a mean age of 35.4 years; 79.6% had moderate-severe endometriosis. Mean scores for overall HRQOL and PCEC were 29.3/100 and 38.0/100, respectively. The PCEC-subscale ‘continuity’ was significantly associated with overall HRQOL (P = 0.029). A significant association was found between overall PCEC and the HRQOL-subscale ‘social support’ (P = 0.026). The PCEC-subscales ‘information’ and ‘continuity’ were significantly associated with the HRQOL-subscales ‘emotional wellbeing’ and ‘social support’ (P < 0.05). The PCEC-subscale ‘respect’ was significantly associated with the HRQOL-subscale ‘emotional wellbeing’ (P = 0.023). Multivariable regression analyses produced no significant associations, including all subscales of PCEC. Providing PCEC could lead to better HRQOL, especially if paying attention to ‘continuity’, ‘respect’ and ‘information’. Large-scale longitudinal research is needed.
J Ultrasound Med. 2017 Nov 30.
Deep Infiltrating Endometriosis: Comparison Between 2-Dimensional Ultrasonography (US), 3-Dimensional US, and Magnetic Resonance Imaging.
To evaluate the diagnostic accuracy of 2-dimensional (2D) and 3-dimensional (3D) transvaginal ultrasonography (US) in comparison with magnetic resonance imaging (MRI) for identification of deep infiltrating endometriosis.
In this prospective observational study, 159 premenopausal women who underwent surgery for a clinical suspicion of deep infiltrating endometriosis were prospectively enrolled. All women underwent 2DUS, 3DUS, and MRI. The following 3 locations of deep endometriosis were considered: (1) intestinal; (2) other posterior lesions (retrocervical septum, rectovaginal septum, uterosacral ligaments, and vaginal fornix); and (3) anterior. The sensitivity, specificity, positive predictive value, and negative predictive value of 2D and 3D transvaginal US in comparison with MRI were determined.
Intestinal deep infiltrating endometriosis was identified by 2DUS in 56 of 66 patients, by 3DUS in 59 of 66, and by MRI in 61 of 66. A receiver operating characteristic curve analysis showed optimal results for 2DUS, 3DUS, and MRI (areas under the curve, 0.86, 0.915, and 0.935, respectively) with a statistically significant difference between 2DUS and MRI (P = .0103), even when the 95% confidence interval showed an overlap. Other posterior deep infiltrating endometriosis was identified by 2DUS in 55 of 75 patients, by 3DUS in 65 of 75, and by MRI in 66 of 75. A receiver operating characteristic curve analysis showed very good results for 2DUS, 3DUS, and MRI (areas under the curve, 0.801, 0.838, and 0.857) with no statistically significant differences. In the 12 women with deep infiltrating endometriosis in the anterior location, the nodules were correctly identified by 2DUS in 3 of 12 patients, by 3DUS in 5 of 12, and by MRI in 6 of 12.
Our results seem to suggest that there is a statistically significant difference between 2DUS and MRI for the intestinal location of deep infiltrating endometriosis, whereas no differences were found among the techniques for the other locations.
Hum Reprod. 2018 Jan 1;33(1):47-57.
Conservative surgery versus colorectal resection in deep endometriosisinfiltrating the rectum: a randomized trial.
Is there a difference in functional outcome between conservative versus radical rectal surgery in patients with large deep endometriosis infiltrating the rectum 2 years postoperatively?
No evidence was found that functional outcomes differed when conservative surgery was compared to radical rectal surgery for deeply invasive endometriosis involving the bowel.
WHAT IS KNOWN ALREADY:
Adopting a conservative approach to the surgical management of deep endometriosis infiltrating the rectum, by employing shaving or disc excision, appears to yield improved digestive functional outcomes. However, previous comparative studies were not randomized, introducing a possible bias regarding the presumed superiority of conservative techniques due to the inclusion of patients with more severe deep endometriosis who underwent colorectal resection.
STUDY DESIGN SIZE, DURATION:
From March 2011 to August 2013, we performed a 2-arm randomized trial, enroling 60 patients with deep endometriosis infiltrating the rectum up to 15 cm from the anus, measuring more than 20 mm in length, involving at least the muscular layer in depth and up to 50% of rectal circumference. No women were lost to follow-up.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Patients were enroled in three French university hospitals and had either conservative surgery, by shaving or disc excision, or radical rectal surgery, by segmental resection. Randomization was performed preoperatively using sequentially numbered, opaque, sealed envelopes, and patients were informed of the results of randomization. The primary endpoint was the proportion of patients experiencing one of the following symptoms: constipation (1 stool/>5 consecutive days), frequent bowel movements (≥3 stools/day), defecation pain, anal incontinence, dysuria or bladder atony requiring self-catheterization 24 months postoperatively. Secondary endpoints were the values of the Visual Analog Scale (VAS), Knowles-Eccersley-Scott-Symptom Questionnaire (KESS), the Gastrointestinal Quality of Life Index (GIQLI), the Wexner scale, the Urinary Symptom Profile (USP) and the Short Form 36 Health Survey (SF36).
MAIN RESULTS AND THE ROLE OF CHANCE:
A total of 60 patients were enroled. Among the 27 patients in the conservative surgery arm, two were converted to segmental resection (7.4%). In each group, 13 presented with at least one functional problem at 24 months after surgery (48.1 versus 39.4%, OR = 0.70, 95% CI 0.22-2.21). The intention-to-treat comparison of the overall scores on KESS, GIQLI, Wexner, USP and SF36 did not reveal significant differences between the two arms. Segmental resection was associated with a significant risk of bowel stenosis.
LIMITATIONS REASONS FOR CAUTION:
The inclusion of only large infiltrations of the rectum does not allow the extrapolation of conclusions to small nodules of <20 mm in length. The presumption of a 40% difference favourable to conservative surgery in terms of postoperative functional outcomes resulted in a lack of power to demonstrate a difference for the primary endpoint.
WIDER IMPLICATIONS OF THE FINDINGS:
Conservative surgery is feasible in patients managed for large deep rectal endometriosis. The trial does not show a statistically significant superiority of conservative surgery for mid-term functional digestive and urinary outcomes in this specific population of women with large involvement of the rectum. There is a higher risk of rectal stenosis after segmental resection, requiring additional endoscopic or surgical procedures.
STUDY FUNDING/COMPETING INTEREST(S):
This work was supported by a grant from the clinical research programme for hospitals (PHRC) in France. The authors declare no competing interests related to this study.
TRIAL REGISTRATION NUMBER:
This study is registered with ClinicalTrials.gov, number NCT 01291576.
TRIAL REGISTRATION DATE:
31 January 2011.
DATE OF FIRST PATIENT’S ENROLMENT:
7 March 2011.
Am J Reprod Immunol. 2018 Feb;79(2).
Analysis of the ectoenzymes ADA, ALP, ENPP1, and ENPP3, in the contents of ovarian endometriomas as candidate biomarkers of endometriosis.
The diagnosis of endometriosis, a prevalent chronic disease with a strong inflammatory component, is usually delayed due to the lack of noninvasive diagnostic tests. Purinergic signaling, a key cell pathway, is altered in many inflammatory disorders. The aim of the present work was to evaluate the levels of adenosine deaminase (ADA), alkaline phosphatase (ALP), ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1), and ENPP3, elements of purinergic signaling, as biomarker candidates for endometriosis.
METHOD OF STUDY:
A case-control comparative study was conducted to determine ADA, ALP, ENPP1 and ENPP3 levels in echo-guided aspirated fluids of endometriomas (case group) and simple ovarian cysts (control group) using the ELISA technique.
Adenosine deaminase, ALP, ENPP1, and ENPP3 were present and quantifiable in the contents of endometriomas and simple cysts. There were significant differences in ADA and ENPP1 levels in endometriomas in comparison with simple cysts (2787 U/L and 103.9 ng/mL more in endometriomas, for ADA and ENPP1, respectively). Comparisons of ALP and ENPP3 levels between the two groups did not reveal significant differences.
The ectoenzymes ADA and ENPP1 are biomarker candidates for endometriosis.
J Minim Invasive Gynecol. 2017 Nov 28.
Laparoscopic Ureteroneocystostomy with a Vesicopsoas Hitch in 10 Steps.
Laparoscopic ureteroneocystostomy with a vesicopsoas hitch has the advantages of a minimally invasive approach. The standardization and description of the technique are the main objectives of this video. We described this procedure in 10 steps, which could help to understand and perform this procedure.
This video presents an approach to laparoscopic ureteroneocystostomy with a vesicopsoas hitch, which was clearly divided into 10 steps. The local institutional review board was consulted and ruled that approval was not required for this video article because the video describes a technique and does not report a clinical case. The patient cannot be identified, and she gave informed consent.
The 10 steps are as follows: step 1, identification of the healthy ureter; step 2, identification of the stenotic part; step 3, section of the ureter; step 4, bladder mobilization; step 5, anterior cystostomy; step 6, psoas hitch; step 7, closure of the anterior cystostomy; step 8, posterior spatulation of the ureter; step 9, cystostomy of the superolateral bladder dome; and step 10, ureteral suture to the bladder.
Laparoscopic ureteroneocystostomy with a vesicopsoas hitch is an effective technique for intrinsic ureteral endometriosis; it usually needs ureteral resection with end-to-end reanastomosis or reimplantation if the anastomosis is in tension. The 10 steps help to perform each part of surgery in logical sequence, making the procedure faster to adopt and learn. The standardization of laparoscopic techniques could help to reduce the learning curve.
Med Ultrason. 2017 Nov 29;19(4):430-437.
Abdominal wall endometriosis: an update in clinical, imagistic features, and management options.
Abdominal wall endometriosis (AWE) is a rare condition defined by the presence of endometrial tissue in the subcutaneous fatty layer and the muscles of the abdominal wall. It is usually caused by the dissemination of endometrial tissue in the wound at the time of obstetrical and gynecological surgeries. AWE is rare and difficult to diagnose. The most frequent clinical presentation is that of a palpable subcutaneous mass near surgical scars associated with cyclic pain and swelling during menses. AWE may be an underreported pathology partly because it has scarcely received attention in the radiologic literature. Its frequency is expected to rise along with the increasing rate of cesarean deliveries; thus, it is important that physicians or sonographers are familiar with this pathology. The purpose of our review is to present the latest data regarding risk factors, clinical and imagisticfindings, and management of AWE.
Fertil Steril. 2018 Jan;109(1):142-147.
Association between surgically diagnosed endometriosis and adverse pregnancy outcomes.
To examine the association between surgically diagnosed endometriosis and pregnancy outcomes in subsequent pregnancies.
Retrospective cohort study of women who delivered a singleton live birth from 2003 to 2013 in Ottawa, Ontario, Canada.
Tertiary level academic center.
Pregnant women with surgically diagnosed endometriosis were identified using International Classification of Diseases-10 codes from previous hospital admissions and were compared with pregnant women with no prior admission for endometriosis for the occurrences of adverse pregnancy outcomes.
MAIN OUTCOME MEASURE(S):
Gestational hypertension, preeclampsia, placenta previa, placental abruption, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and neonatal intensive care unit admission.
Among the 52,202 eligible mother-infant pairs, we identified 469 mothers with surgically diagnosed endometriosis from a previous hospital encounter. Compared with women without endometriosis, women with endometriosis were on average older and were more likely to be primiparous, have lower gravidity, have a history spontaneous abortion, conceive with assisted reproductive technology, and reside in areas with higher neighborhood income and lower proportion of immigrants. Women with endometriosis were found to have an elevated risk of placenta previa (relative risk [RR], 3.30; 95% confidence interval [CI], 1.65-5.40) and cesarean delivery (RR, 1.24; 95% CI, 1.10-1.40). After adjustment for potential confounding factors, women with endometriosis were found to have a significantly elevated risk of placenta previa compared with women without endometriosis (adjusted RR, 2.54; 95% CI, 1.39-4.64).
This study identifies baseline demographic differences between women with and without endometriosis and suggests that women affected by endometriosis have an independently elevated risk of placenta previa in pregnancy.
Diagnostics of endometriosis by using magnetic resonance imaging.
Endometriosis affects about 2 to 10% of women in fertile age, It causes pain and infertility. In the ovaries, endometrios causes endometriomas. The disease may spread into the abdominal cavity and even result in ileus. Deep endometriomas are located under the peritoneal surface, typically behind the uterus and in the region of uterosacral ligaments. History, clinical examination and transvaginal ultrasound scanning usually lead to the diagnosis. Magnetic resonance imaging is in particular utilized prior to surgery. It provides a comprehensive view of endometriosis lesions in the pelvis, including deep foci.
Exp Ther Med. 2017 Nov;14(5):4647-4654.
Protein-protein interaction analysis to identify biomarker networks for endometriosis.
The identification of biomarkers and their interaction network involved in the processes of endometriosis is a critical step in understanding the underlying mechanisms of the disease. The aim of the present study was to construct biomarker networks of endometriosis that integrated human protein-protein interactions and known disease-causing genes. Endometriosis-associated genes were extracted from Genotator and DisGeNet and biomarker network and pathway analyses were constructed using atBioNet. Of 100 input genes, 96 were strongly mapped to six major modules. The majority of the pathways in the first module were associated with the proliferation of cancer cells, the enriched pathways in module B were associated with the immune system and infectious diseases, module C included pathways related to immune and metastasis, the enriched pathways in module D were associated with inflammatory processes, and the majority of the pathways in module E were related to replication and repair. The present approach identified known and potential biomarkers in endometriosis. The identified biomarker networks are highly enriched in biological pathways associated with endometriosis, which may provide further insight into the molecular mechanisms underlying endometriosis.
Exp Ther Med. 2017 Nov;14(5):4846-4852..
miR-30c may serve a role in endometriosis by targeting plasminogen activator inhibitor-1.
The present study aimed to investigate the role of miR-30c in endometriosis (EMs) and the underlying mechanism. The expression of miR-30c and plasminogen activator inhibitor type 1 (PAI-1) mRNA in EMs tissues was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and the expression of PAI-1 protein was detected by western blot analysis. The proliferation, migration, invasion and adhesion of endometrial stromal cells (ESCs) in different groups transfected with miR-30c mimic or inhibitor were compared. It was demonstrated that miR-30c expression in ectopic and eutopic endometriosis tissues were significantly lower than in normal endometrial tissue. However, PAI-1 mRNA expression in ectopic and eutopic endometrial tissues was higher than in normal endometrial tissues. Furthermore, the expression of PAI-1 protein was higher in ectopic and eutopic endometrosis tissues than in normal tissues. RT-qPCR results indicated that miR-30c expression was significantly increased or decreased in ESCs following transfection of mimic or inhibitor of miR-30c, respectively. Overexpression of miR-30c repressed the expression of PAI-1 mRNA and protein, while inhibition of miR-30c upregulated the expression of PAI-1 in ESCs. In addition, the invasion, migration, proliferation and adhesion of ESCs was repressed following the overexpression of miR-30c, whereas they were promoted when miR-30c expression was downregulated. The results of the present study indicated that miR-30c serves an important role in the development and progression of EMs by regulating the expression of PAI-1.
Fertil Steril. 2017 Dec;108(6):1016-1025.e2.
Serum galectin-9 as a noninvasive biomarker for the detection of endometriosis and pelvic pain or infertility-related gynecologic disorders.
To investigate the usefulness of soluble galectin-9 (Gal-9) in the noninvasive laboratory diagnosis of endometriosis and various gynecologic disorders.
Prospective case-control study.
University medical centers.
A total of 135 women of reproductive age were involved in the study, 77 endometriosispatients, 28 gynecologic controls, and 30 healthy women.
Diagnostic laparoscopy and collection of tissue biopsies, peritoneal cells, and native peripheral blood from different case groups of gynecology patients and healthy women.
MAIN OUTCOME MEASURE(S):
The expression of mRNA and serum concentration of Gal-9.
Semiquantitative reverse transcription-polymerase chain reaction analysis and serum soluble Gal-9 ELISA were performed on three different cohorts of patients: those with endometriosis, those with benign gynecologic disorders, and healthy controls. Differences in the Gal-9 concentrations between the investigated groups and the stability of Gal-9 in the serum and diagnostic characteristics of Gal-9 ELISA were determined by statistical evaluation and receiver operating characteristic (ROC) curve analysis. Significantly elevated Gal-9 levels were found in both minimal-mild (I-II) and moderate-severe (III-IV) stages of endometriosis in comparison with healthy controls. At a cutoff of 132 pg/mL, ROC analysis revealed an excellent diagnostic value of Gal-9 ELISA in endometriosis (area under the curve = 0.973) with a sensitivity of 94% and specificity of 93.75%, indicating better diagnostic potential than that of other endometriosisbiomarkers. Furthermore, various pelvic pain or infertility-associated benign gynecologic conditions were also associated with increased serum Gal-9 levels.
Our results suggest that Gal-9 could be a promising noninvasive biomarker of endometriosis and a predictor of various infertility or pelvic pain-related gynecologic disorders.
Fertil Steril. 2017 Dec;108(6):869-871.
Introduction: From pathogenesis to therapy, deep endometriosis remains a source of controversy.
Deep endometriosis remains a source of controversy. A number of theories may explain its pathogenesis and many arguments support the hypothesis that genetic or epigenetic changes are a prerequisite for development of lesions into deep endometriosis. Deep endometriosis is frequently responsible for pelvic pain, dysmenorrhea, and/or deep dyspareunia, but can also cause obstetrical complications. Diagnosis may be improved by high-quality imaging. Therapeutic approaches are a source of contention as well. In this issue’s Views and Reviews, medical and surgical strategies are discussed, and it is emphasized that treatment should be designed according to a patient’s symptoms and individual needs. It is also vital that referral centers have the knowledge and experience to treat deep endometriosis medically and/or surgically. The debate must continue because emerging trends in therapy need to be followed and investigated for optimal management.
Fertil Steril. 2017 Dec;108(6):886-894.
Diagnosis of deep endometriosis: clinical examination, ultrasonography, magnetic resonance imaging, and other techniques.
The aim of the present review was to evaluate the contribution of clinical examination and imaging techniques, mainly transvaginal sonography and magnetic resonance imaging (MRI) to diagnose deep infiltrating (DE) locations using prisma statement recommendations. Clinical examination has a relative low sensitivity and specificity to diagnose DE. Independently of DE locations, for all transvaginal sonography techniques a pooled sensitivity and specificity of 79% and 94% are observed approaching criteria for a triage test. Whatever the protocol and MRI devices, the pooled sensitivity and specificity for pelvic endometriosis diagnosis were 94% and 77%, respectively. For rectosigmoid endometriosis, pooled sensitivity and specificity of MRI were 92% and 96%, respectively fulfilling criteria of replacement test. In conclusion, advances in imaging techniques offer high sensitivity and specificity to diagnose DE with at least triage value and for rectosigmoid endometriosis replacement value imposing a revision of the concept of laparoscopy as the gold standard.
Fertil Steril. 2017 Dec;108(6):895-912.
Obstetrical complications of endometriosis, particularly deep endometriosis.
Over the past few years, a new topic in the field of endometriosis has emerged: the potential impact of the disease on pregnancy outcomes. This review aims to summarize in detail the available evidence on the relationship between endometriosis, particularly deep endometriosis (DE), and obstetrical outcomes. Acute complications of DE, such as spontaneous hemoperitoneum, bowel perforation, and uterine rupture, may occur during pregnancy. Although these events represent life-threatening conditions, they are rare and unpredictable. Therefore, the current literature does not support any kind of prophylactic surgery before pregnancy to prevent such complications. Results on the impact of DE on obstetrical outcomes are debatable and characterized by several limitations, including small sample size, lack of adjustment for confounders, lack of adequate control subjects, and other methodologic flaws. For these reasons, it is not possible to draw conclusions on this topic. The strongest evidence shows that DE is associated with higher rates of placenta previa; for other obstetrical outcomes, such as miscarriage, intrauterine growth restriction, preterm birth and hypertensive disorders, results are controversial. Although it is unlikely that surgery of DE may modify the impact of the disease on the course of pregnancy, no study has yet investigated this issue.
Fertil Steril. 2017 Dec;108(6):913-930.
Role of medical therapy in the management of deep rectovaginal endometriosis.
Defining whether medical therapy is effective in women with deep rectovaginal endometriosis and in which circumstances it can be considered an alternative to surgery is important for patients and physicians. Numerous observational and some randomized controlled studies demonstrated that different hormonal drugs improved pain and other symptoms in approximately two-thirds of women with deep rectovaginal endometriosis. Because major differences in the effect size of various compounds were not observed, much importance should be given to safety, tolerability, and cost of medications when counseling patients. Progestins seem to offer the best therapeutic balance when long-term treatments are planned. Women should be informed that hormonal drugs control but do not cure endometriosis and that, to avoid surgery, they should be used for years. Medical therapy is not an alternative to surgery in women with hydronephrosis, severe subocclusive bowel symptoms, and in those wishing a natural conception. A progestin should systematically be chosen as a comparator in future randomized trials on novel medications for deep endometriosis. In the meantime, the use of existing drugs should be optimized, and medical and surgical treatments could be viewed as subsequent stages of a stepwise approach. In general, there is no absolute “best” choice, and women must be thoroughly informed of potential benefits, potential harms, and costs of different therapeutic options and allowed to choose what they deem is better for them.
Fertil Steril. 2017 Dec;108(6):931-942.
Choosing the right surgical technique for deep endometriosis: shaving, disc excision, or bowel resection?
Deep endometriosis (DE) remains the most difficult endometriotic entity to treat. Medical treatment for DE can reduce symptoms but does not cure the disease, and surgical removal of the lesion is required when lesions are symptomatic, impairing bowel, urinary, sexual, and reproductive functions. Although several surgical techniques such as laparoscopic bowel resection, disc excision, and rectal shaving have been described, there is no consensus regarding the choice of technique or the timing of surgery. Our review of publications reporting results and complications of surgery for rectovaginal DE reveals a relatively higher complication rate after bowel resection compared with shaving and disc excision, especially for rectovaginal fistulas, anastomotic leakage, delayed hemorrhage, and long-term bladder catheterization. Data show that shaving is feasible even in advanced disease. The risk of immediate complications after shaving and disc excision is probably lower than after colorectal resection, allowing for better functional outcomes. The presumed higher risk of recurrence related to shaving has not been demonstrated. For these reasons, surgeons should consider rectal shaving as a first-line surgical treatment of rectovaginal DE, regardless of nodule size or association with other digestive localizations. When the result of rectal shaving is unsatisfactory (rare cases), disc excision may be performed either exclusively by laparoscopy or by using transanal staplers. Segmental resection may ultimately be reserved for advanced lesions responsible for major stenosis or for several cases of multiple nodules infiltrating the rectosigmoid junction or sigmoid colon.