J Manag Care Spec Pharm. 2016 May;22(5):573-87.

Analysis of Adherence, Persistence, and Surgery Among EndometriosisPatients Treated with Leuprolide Acetate Plus Norethindrone Acetate Add-Back Therapy.

Soliman AM1Bonafede M2Farr AM2Castelli-Haley J1Winkel C3.

 

Abstract

BACKGROUND:

Endometriosis affects over 10 million women in the United States. Depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, has been used extensively for the treatment of women with endometriosis but is associated with hypoestrogenic symptoms and bone mineral density loss. The concomitant use of add-back therapies, specifically norethindrone acetate (NETA), can alleviate these adverse effects.

OBJECTIVE:

To compare adherence to and persistence with LA treatment and time to endometriosis-related surgery among women treated with NETA and women treated with LA plus other add-back therapies or LA only.

METHODS:

This retrospective analysis was conducted using Truven Health MarketScan Commercial Claims and Encounters Database. Women with a diagnosis of endometriosis (ICD-9-CM code 617.xx) who initiated LA (index date) in 2005-2011 were selected for inclusion. Additional requirements were 12 months of continuous enrollment pre- and post-index and no evidence of endometriosis-related surgeries pre-index or up to 30 days post-index; no pre-index use of estrogen or noncontraceptive hormones; and no diagnoses of uterine fibroids, malignant neoplasms, infertility, or pregnancy. Patients were characterized as using NETA; other add-back therapies (estrogens, progestins, or estrogen-progestin combinations); or no add-back therapy. Adherence to and persistence with LA were measured over the 6 months following the index date using outpatient medical and pharmacy claims. Patients were considered adherent if their proportion of days covered was greater than or equal to 0.80. Persistence was operationalized as time to discontinuation, defined as a continuous gap of > 60 days without LA on hand. Time to endometriosis-related surgery (laparotomy, laparoscopy, excision/ablation/fulguration, oophorectomy, and hysterectomy) was measured over the 12 months following the index date. Surgeries were identified from inpatient and outpatient medical claims using procedure codes. Outcomes were compared among cohorts using multivariable logistic and Cox proportional hazards regression models controlling for demographics and baseline clinical characteristics.

RESULTS:

The final sample included 3,114 women, with a mean age of 36.9 years. The majority of women used LA only with no add-back therapy (n = 1,963, 63.0%), while 15.1% (n = 470) used NETA, and 21.9% (N = 681) used other add-back therapies. During the 6-month follow-up, more patients in the LA plus NETA cohort were adherent to LA therapy compared with LA only (47.2% vs. 31.5%, P < 0.001), and fewer patients discontinued (37.9% vs. 59.6%, P < 0.001). Additionally, fewer patients underwent endometriosis-related surgery in the 12 months after LA initiation in the LA plus NETA cohort (12.6% vs. 16.9%, P = 0.021). In multivariable models, women who initiated LA plus NETA or LA plus other add-back therapies had a higher likelihood of being adherent to LA than LA only patients (OR = 1.91, 95% CI = 1.55-2.36 and OR = 1.95, 95% CI = 1.63-2.34) and lower likelihood of LA discontinuation (HR = 0.54, 95% CI = 0.46-0.63 and HR = 0.59, 95% CI = 0.52-0.68). NETA patients had a lower surgery rate in the 12-month post-index period compared with other add-back patients (HR = 0.68, 95% CI = 0.50-0.93) or LA only patients (HR = 0.69, 95% CI = 0.52-0.92).

CONCLUSIONS:

For women with endometriosis, treatment with LA and concomitant add-back therapies was associated with better adherence to and persistence with LA over the 6 months following initiation, compared with treatment with LA only. The increased adherence and persistence to LA may translate into decreased need for surgical intervention, although fewer endometriosis-related surgeries were only observed in the 12 months following LA initiation for patients using concomitant NETA add-back therapy. These results support an increased and earlier use of NETA add-back therapy among women who initiate LA.

DISCLOSURES:

This study was funded by AbbVie, which also markets the endometriosis drugs Lupron and Lupaneta Pack. AbbVie participated in the study design, research, data collection, analysis and interpretation, writing, review, and approval of this publication. Soliman and Castelli-Haley are employees of AbbVie and may own AbbVie stock or stock options. Bonafede and Farr are employees of Truven Health Analytics, which received a research contract to conduct this study with and on behalf of AbbVie. Winkel is a clinical professor in the Department of Obstetrics and Gynecology at Georgetown University in Washington, DC, and has served in a consulting role on research to AbbVie for this project. An earlier version of the current research was presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 20th Annual International Meeting; Philadelphia, PA; May 2015. All authors participated in data analysis and interpretation and contributed to the development of the manuscript.

 

 

Taiwan J Obstet Gynecol. 2016 Apr;55(2):251-7.

Vitamin C is effective for the prevention and regression of endometriotic implants in an experimentally induced rat model of endometriosis.

Erten OU1Ensari TA2Dilbaz B3Cakiroglu H4Altinbas SK3Çaydere M5Goktolga U3.

 

Abstract

OBJECTIVE:

Endometriosis is a chronic inflammatory disease pathologically defined as the presence of endometrial-like tissue outside the uterine cavity. It is one of the most important diseases affecting women of reproductive age. The process of endometriotic implant growth is mediated by many complex interactions of immunologic, hormonal, genetic, and environmental mediators. Vitamin C (ascorbic acid), besides playing a role in preventing invasion and metastasis, is an antioxidant having anti-inflammatory and -angiogenic effects. In this study, we aimed to investigate the effect of vitamin C on the prevention and regression of endometriotic implants in a rat model of endometriosis.

MATERIALS AND METHODS:

This was a prospective, comparative, experimental animal study. After endometriotic implants were induced simultaneously, rats were divided into three groups. Group A was given 500 mg/kg of intravenous vitamin C every 2 days, starting immediately after implantation (n = 11). All rats had a second operation 21 days after the initial one and had the lesion volumes measured. Group B was given 500 mg/kg of intravenous vitamin C every 2 days, starting 21 days after this operation (n = 11). All rats were sacrificed 21 days after the third operation. Implant volume, weight measurements, and histopathological evaluation of the lesions were carried out. Group A received vitamin C throughout the study, while Group C (n = 11) was not given any medication. The findings in the three groups were compared.

RESULTS:

At the second laparotomy after the induction, Group A had the smallest implant volume with a statistically significant difference compared to Group B (p = 0.012). The end-of-study volumes of endometriotic implants of group B were significantly smaller than the first volumes (p < 0.05).

CONCLUSION:

Intravenous vitamin C treatment might have a suppressive effect on the prevention of endometriotic implant induction and regression of endometriotic implant volumes.

 

 

Mater Sci Eng C Mater Biol Appl. 2016 Jul 1;64:310-317.

Development and pharmacological evaluation of in vitro nanocarriers composed of lamellar silicates containing copaiba oil-resin for treatment of endometriosis.

de Almeida Borges VR1da Silva JH2Barbosa SS1Nasciutti LE2Cabral LM1de Sousa VP3.

 

Abstract

In this work, newly developed nanocomposites based upon lamellar silicates are evaluated to determine their potential in controlling endometriosis. The preparation of the new nanocarriers is detailed, properties characterized and in vitro pharmacological evaluation performed. The nanocomposites in this study were obtained from the reaction of copaiba oil-resin (COPA) with the polymer polyvinylpyrrolidone (PVP K-30). COPA was selected due to its antiinflammatory and anticancer activities along with the organophilic derivatives of sodium montmorillonite, Viscogel B8, S7 and S4. The results indicated that it was feasible to obtain a good yield of a COPA nanocomposite using a simple process. Intercalation was confirmed by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). In vitro release experiments demonstrated that COPA was released from the nanocomposite in a delayed fashion. Whereas, in vitro pharmacological studies showed a reduction in viability and proliferation of endometriotic cell cultures upon COPA nanocomposite treatment, suggesting that the system developed here can be a promising alternative therapy for the oral treatment of endometriosis.

 

 

J Reprod Immunol. 2016 Aug;116:1-6.

Promotion of angiogenesis and proliferation cytokines patterns in peritoneal fluid from women with endometriosis.

Rakhila H1Al-Akoum M1Bergeron ME2Leboeuf M2Lemyre M2Akoum APouliot M3.

 

Abstract

Studies have long sought specific cytokines that could characterize endometriosis. Either due to variations between study designs regarding the assessment criteria for the cytokine or to low power resulting from small sample size, no factor proved to be sufficiently specific to endometriosis. In other clinical fields, a combination of several markers proved to be more powerful than a single-molecule approach. As well, in the context of endometriosis, simultaneous assessment of several cytokines present in the peritoneal fluid might help in unveiling patho-physiological processes, thus contributing to a better understanding of the condition. Therefore, the objective of this study was to investigate peritoneal fluid cytokines-derived of endometriotic women. For this retrospective case-control study, peritoneal fluid samples were obtained at laparoscopy and assessed by multiplex. Our data showed distinct patterns of peritoneal fluid cytokine concentrations in endometriotic women most notably a marked increase in EGF, FGF-2, IL-1α, MIP-1β, TGFα, PDGF-AA, PDGF-BB, MCP-3, sCD40L, Gro Pan, IL-17α, MDC and Rantes. The overall effect of fertility status revealed a significant difference for only one cytokine, namely MDC. Furthermore, FLT-3L and IP-10 levels were decreased in endometriosis patients, the former in both menstrual cycle phases and the latter in the secretory phase. A significant inverse Pearson correlation (p<0.05) was noted between pro-angiogenic cytokines EGF and FGF and the anti-angiogenic cytokine IP-10 in endometriosis patients at stages III-IV and in the secretory phase. These changes may exacerbate the local peritoneal angiogenic and proliferative reaction observed in women with endometriosis, and contributes to its pathophysiology.

 

 

Eur J Radiol. 2016 May;85(5):1016-9

Computed diffusion-weighted imaging for differentiating decidualized endometrioma from ovarian cancer.

Takeuchi M1Matsuzaki K2Harada M3.

 

Abstract

PURPOSE:

To evaluate the clinical diagnostic ability of computed diffusion-weighted imaging (DWI) for differentiating decidualized endometrioma from ovarian cancer.

MATERIALS AND METHODS:

Computed DWI technique was retrospectively applied to 20 mural nodules in 9 decidualized endometriomas during pregnancy and 20 ovarian cancers. Signal intensities on measured DWI with b values of 800s/mm(2) (DWI800) and on computed DWI with b values of 1500s/mm(2) (cDWI1500) were visually evaluated.

RESULTS:

Mural nodules of all decidualized endometriomas showed high signal intensity on DWI800 with significantly higher ADC (2.01±0.26×10(-3)mm(2)/s) and low signal intensity on cDWI1500, whereas solid components of all ovarian cancers showed high signal intensity on both DWI800 with lower ADC (1.08±0.20×10(-3)mm(2)/s) and on cDWI1500.

CONCLUSION:

Mural nodules in decidualized endometriomas may show high signal intensity on DWI800 due to T2 shine-through effect, and cDWI1500 can distinguish decidualized endometriomas from ovarian cancers by visual evaluation.

 

 

 

 

 

Reprod Sci. 2016 Nov;23(11):1526-1535.

Emodin Inhibits Migration and Invasion of Human Endometrial Stromal Cells by Facilitating the Mesenchymal-Epithelial Transition Through Targeting ILK.

Zheng Q1Xu Y1Lu J1Zhao J1Wei X1Liu P2.

 

Abstract

OBJECTIVE:

To determine whether emodin facilitates the mesenchymal-epithelial transition (MET) of endometrial stromal cells (ESCs) as well as to explore the mechanism through which emodin favored the MET of ESCs.

METHODS:

Cell viability was tested by methyl thiazolyl tetrazolium assay. Cell migration and invasion abilities were detected by transwell assays. Levels of integrin-linked kinase (ILK) and epithelial-mesenchymal transition (EMT)-related proteins were detected by Western blot.

RESULTS:

Upregulated ILK and increased abilities of migration and invasion were confirmed in the eutopic and ectopic ESCs (EuSCs and EcSCs), especially in the EcSCs. After treated with emodin, the expression of ILK was statistically downregulated in EcSCs, resulting in the MET and decreased migration and invasion abilities of EcSCs. Additionally, silencing of the ILK gene in EcSCs also achieved the above-mentioned effects, which were strengthened by emodin. Furthermore, exogenous expression of ILK in control ESCs (CSCs) resulted in the EMT and increased abilities of migration and invasion of CSCs, which can be abrogated by emodin. Besides, exogenous expression of ILK also abrogated the effects of emodin on CSCs.

CONCLUSION:

Emodin inhibits the migration and invasion abilities of human ESCs by facilitating the MET through targeting ILK.

 

 

J Minim Invasive Gynecol. 2016 Jul-Aug;23(5):839-42.

Continuous Amenorrhea May Be Insufficient to Stop the Progression of Colorectal Endometriosis.

Millochau JC1Abo C1Darwish B1Huet E2Dietrich G1Roman H3.

 

Abstract

We present the case of a patient in whom consecutive imaging assessment and surgery demonstrated the obvious progression of colorectal endometriosis under continuous medical therapy. A 26-year-old nullipara presented with secondary dysmenorrhea, deep dyspareunia, diarrhea, and constipation during menstruation. Magnetic resonance imaging (MRI) assessment revealed 2 right ovarian endometriomas, but no deep endometriosis lesion. Intraoperatively, we found a 2-cm length of thickened and congestive area of sigmoid colon, along with small superficial lesions arising in the small bowel and appendix. We performed ablation of ovarian endometriomas and appendectomy, and decided to not resect the bowel. Postoperative computed tomography-based virtual colonoscopy (CTC) revealed a slight abnormality of the sigmoid colon. Endorectal ultrasound identified a normal rectum and sigmoid colon. Despite long-term continuous medical treatment, the patient presented 4 years later with impaired digestion consisting in constipation alternating with diarrhea, bloating, dyschesia, and pelvic pain. MRI and CTC revealed an abnormal sigmoid colon from 42 to 50 cm above the anus, with digestive tract diameter reduced from 10 mm down to the virtual lumen, along with an overall rigid appearance. Laparoscopy revealed the extent of endometriosis lesions in the sigmoid colon and multiple implantations in the small bowel. We performed sigmoid and small bowel resection. This case demonstrates the obvious progression of deep rectal endometriosisdespite 4 years of continuous hormonal therapy.

 

 

Hum Reprod. 2016 Aug;31(8):1765-75.

Endometriosis-related infertility: ovarian endometrioma per se is not associated with presentation for infertility.

Santulli P1Lamau MC2Marcellin L3Gayet V2Marzouk P2Borghese B4Lafay Pillet MC2Chapron C5.

 

Abstract

STUDY QUESTION:

Is there an association between the endometriosis phenotype and presentation with infertility?

SUMMARY ANSWER:

In a population of operated patients with histologically proven endometriosis, ovarian endometrioma (OMA) per se is not associated with an increased risk of presentation with infertility, while previous surgery for endometriosis was identified as a risk factor for infertility.

WHAT IS KNOWN ALREADY:

The increased prevalence of endometriosis among subfertile women indicates that endometriosis impairs reproduction for reasons that are not completely understood.

STUDY DESIGN, SIZE, DURATION:

This was an observational, cross-sectional study using data prospectively collected in all non-pregnant patients aged between 18 and 42 years, who were surgically explored for benign gynaecological conditions at our institution between January 2004 and March 2013. For each patient, a standardized questionnaire was completed during a face-to-face interview conducted by the surgeon during the month preceding surgery.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Surgery was performed in 2208 patients, of which 2066 signed their informed consent. Of the 1059 women with a visual diagnosis of endometriosis, 870 had histologically proven endometriosis and complete treatment for their endometriotic lesions, including 307 who presented with infertility. Univariate analysis and multiple logistic regression analysis were performed to determine factors associated with infertility.

MAIN RESULTS AND THE ROLE OF CHANCE:

The following variables were identified as risk factors for endometriosis-related infertility: age >32 years (odds ratio [OR] = 1.9; 95% confidence interval [CI]: 1.4-2.4), previous surgery for endometriosis (OR = 1.9; 95% CI: 1.3-2.2), as well as peritoneal superficial endometriosis (OR = 3.1; 95% CI: 1.9-4.9); Conversely, previous pregnancy was associated with a lower rate of infertility (OR = 0.7; 95% CI: 0.6-0.9 and OR = 0.6; 95% CI: 0.4-0.9, respectively). OMA is not selected as a significant risk factor for infertility.

LIMITATIONS, REASON FOR CAUTION:

The selection of our study population was based on a surgical diagnosis. We cannot exclude that infertile women with OMA associated with a diminished ovarian reserve, as assessed during their infertility work-up, were referred less frequently to surgery and might therefore be underrepresented. In addition we cannot exclude that our group of infertile women present associated other causes of infertility.

WIDER IMPLICATIONS OF THE FINDINGS:

Identification of risk and preventive factors of endometriosis-related infertility can help improve clinical and surgical management of endometriosis in the setting of infertility.

 

 

Hum Reprod. 2016 Jul;31(7):1462-74.

Platelet-derived TGF-β1 mediates the down-modulation of NKG2D expression and may be responsible for impaired natural killer (NK) cytotoxicity in women with endometriosis.

Guo SW1Du Y2Liu X3.

 

Abstract

STUDY QUESTION:

Does platelet-derived transforming growth factor-β1 (TGF-β1) have any role in the reduced cytotoxicity of natural killer (NK) cells in women with endometriosis?

SUMMARY ANSWER:

Platelet-derived TGF-β1 suppresses the expression of NK Group 2, Member D (NKG2D) on NK cells, resulting in reduced cytotoxicity in women with endometriosis, but neutralization of TGF-β1 reverses the reduction.

WHAT IS KNOWN ALREADY:

NK cells are cytotoxic lymphocytes that play an important role in peritoneal immune surveillance, and their function is known to be impaired in women with endometriosis. There is increased platelet aggregation in endometriotic lesions and increased platelet activation rate in the peripheral blood in women with endometriosis, yet activated platelets release copiousTGF-β1, which is known to be a potent immunosuppressive molecule that suppresses NK cell function and NKG2D expression.

STUDY DESIGN, SIZE, DURATION:

Cross-sectional clinical studies of 30 women with endometriosis and 33 women without endometriosis and in vitro experimentation with and without TGF-β1 blockade.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Peritoneal fluid (PF) samples from premenopausal women with endometriosis and age- and menstrual phase-matched controls were collected. Platelet count, white blood cell (WBC) count, mean platelet volume (MPV), platelet activation rate, TGF-β1 concentration, expression levels of NKG2D on NK cells in the PF were evaluated. The apoptosis of freshly isolated NK cells treated with PF from women with endometriosis, the NK cytotoxicity and NKG2D expression treated with PF in the presence or absence of an anti-TGF-β1 antibody were also determined.

MAIN RESULTS AND THE ROLE OF CHANCE:

The platelet count, WBC count, MPV, platelet activation rate and the TGF-β1 concentration in the PF from women with endometriosis were significantly elevated when compared with those of women without endometriosis. The TGF-β1 concentration correlated positively with the platelet activation rate (r = 0.59, P < 0.01), suggesting that activated platelets are responsible, at least in part, for the increased TGF-β1 concentration. The cytotoxicity of freshly isolated NK cells treated with PF of women with endometriosis is significantly reduced when compared with that of women without endometriosis. Both the platelet activation rate and the TGF-β1 concentration in the PF correlated negatively with the NKG2D expression in NK cells isolated from the PF (r = -0.36, P < 0.01, and r = -0.45, P < 0.01, respectively). In addition, the NKG2D expression level and the cytotoxicity in freshly isolated NK cells were found to be significantly reduced if co-cultured with PF from women with endometriosis, but the TGF-β1 blockade effectively reverses the reduction.

LIMITATIONS, REASONS FOR CAUTION:

This study is limited by the cross-sectional nature of the study.

WIDER IMPLICATIONS OF THE FINDINGS:

NKG2D is known to potently activate NK cells, so potent that it even overrides inhibitory signals transduced by other inhibitory receptors. This is the first time we demonstrate that platelet-derived TGF-β1 may be responsible for reduced NKG2D expression as well as reduced cytotoxicity of NK cells in women with endometriosis. This study provides yet another piece of evidence that platelets play critical roles in the development of endometriosis, and anti-platelet treatment should improve NK cell functionality in treating endometriosis. Equally important, this study highlights the critical role of the lesion microenvironment in shaping NK cell-mediated anti-endometriotic immunity.

 

 

Cochrane Database Syst Rev. 2016 May 1;(5):

Blood biomarkers for the non-invasive diagnosis of endometriosis.

Nisenblat V1Bossuyt PMShaikh RFarquhar CJordan VScheffers CSMol BWJohnson NHull ML.

 

Abstract

BACKGROUND:

About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis. Although other reviews have assessed the ability of blood tests to diagnose endometriosis, this is the first review to use Cochrane methods, providing an update on the rapidly expanding literature in this field.

OBJECTIVES:

To evaluate blood biomarkers as replacement tests for diagnostic surgery and as triage tests to inform decisions on surgery for endometriosis. Specific objectives include:1. To provide summary estimates of the diagnostic accuracy of blood biomarkers for the diagnosis of peritoneal, ovarian and deep infiltrating pelvic endometriosis, compared to surgical diagnosis as a reference standard.2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses.

SEARCH METHODS:

We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as these databases to 20 April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.

SELECTION CRITERIA:

We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more blood biomarkers with the findings of surgical visualisation of endometriotic lesions.

DATA COLLECTION AND ANALYSIS:

Two authors independently collected and performed a quality assessment of data from each study. For each diagnostic test, we classified the data as positive or negative for the surgical detection of endometriosis, and we calculated sensitivity and specificity estimates. We used the bivariate model to obtain pooled estimates of sensitivity and specificity whenever sufficient datasets were available. The predetermined criteria for a clinically useful blood test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of ≥ 0.95 and a specificity of ≥ 0.50, which ‘rules out’ the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of ≥ 0.50 and a specificity of ≥ 0.95, which ‘rules in’ the diagnosis with high accuracy if there is a positive result (SpIN test).

MAIN RESULTS:

We included 141 studies that involved 15,141 participants and evaluated 122 blood biomarkers. All the studies were of poor methodological quality. Studies evaluated the blood biomarkers either in a specific phase of the menstrual cycle or irrespective of the cycle phase, and they tested for them in serum, plasma or whole blood. Included women were a selected population with a high frequency of endometriosis (10% to 85%), in which surgery was indicated for endometriosis, infertility work-up or ovarian mass. Seventy studies evaluated the diagnostic performance of 47 blood biomarkers for endometriosis (44 single-marker tests and 30 combined tests of two to six blood biomarkers). These were angiogenesis/growth factors, apoptosis markers, cell adhesion molecules, high-throughput markers, hormonal markers, immune system/inflammatory markers, oxidative stress markers, microRNAs, tumour markers and other proteins. Most of these biomarkers were assessed in small individual studies, often using different cut-off thresholds, and we could only perform meta-analyses on the data sets for anti-endometrial antibodies, interleukin-6 (IL-6), cancer antigen-19.9 (CA-19.9) and CA-125. Diagnostic estimates varied significantly between studies for each of these biomarkers, and CA-125 was the only marker with sufficient data to reliably assess sources of heterogeneity.The mean sensitivities and specificities of anti-endometrial antibodies (4 studies, 759 women) were 0.81 (95% confidence interval (CI) 0.76 to 0.87) and 0.75 (95% CI 0.46 to 1.00). For IL-6, with a cut-off value of > 1.90 to 2.00 pg/ml (3 studies, 309 women), sensitivity was 0.63 (95% CI 0.52 to 0.75) and specificity was 0.69 (95% CI 0.57 to 0.82). For CA-19.9, with a cut-off value of > 37.0 IU/ml (3 studies, 330 women), sensitivity was 0.36 (95% CI 0.26 to 0.45) and specificity was 0.87 (95% CI 0.75 to 0.99).Studies assessed CA-125 at different thresholds, demonstrating the following mean sensitivities and specificities: for cut-off > 10.0 to 14.7 U/ml: 0.70 (95% CI 0.63 to 0.77) and 0.64 (95% CI 0.47 to 0.82); for cut-off > 16.0 to 17.6 U/ml: 0.56 (95% CI 0.24, 0.88) and 0.91 (95% CI 0.75, 1.00); for cut-off > 20.0 U/ml: 0.67 (95% CI 0.50 to 0.85) and 0.69 (95% CI 0.58 to 0.80); for cut-off > 25.0 to 26.0 U/ml: 0.73 (95% CI 0.67 to 0.79) and 0.70 (95% CI 0.63 to 0.77); for cut-off > 30.0 to 33.0 U/ml: 0.62 (95% CI 0.45 to 0.79) and 0.76 (95% CI 0.53 to 1.00); and for cut-off > 35.0 to 36.0 U/ml: 0.40 (95% CI 0.32 to 0.49) and 0.91 (95% CI 0.88 to 0.94).We could not statistically evaluate other biomarkers meaningfully, including biomarkers that were assessed for their ability to differentiate endometrioma from other benign ovarian cysts.Eighty-two studies evaluated 97 biomarkers that did not differentiate women with endometriosis from disease-free controls. Of these, 22 biomarkers demonstrated conflicting results, with some studies showing differential expression and others no evidence of a difference between the endometriosis and control groups.

AUTHORS’ CONCLUSIONS:

Of the biomarkers that were subjected to meta-analysis, none consistently met the criteria for a replacement or triage diagnostic test. A subset of blood biomarkers could prove useful either for detecting pelvic endometriosis or for differentiating ovarian endometrioma from other benign ovarian masses, but there was insufficient evidence to draw meaningful conclusions. Overall, none of the biomarkers displayed enough accuracy to be used clinically outside a research setting. We also identified blood biomarkers that demonstrated no diagnostic value in endometriosis and recommend focusing research resources on evaluating other more clinically useful biomarkers.

 

 

Clin Exp Obstet Gynecol. 2016;43(2):254-7.

-1195 A/G promoter variants of the cyclooxygenase-2 gene increases the risk of pain occurrence in endometriotic women.

Wang HSun LJiang MLiu LWang G.

 

Abstract

OBJECTIVE:

The aim of this study was to evaluate the association between -1195 A/G polymorphism in cyclooxygenase-2 (COX-2) gene and the risk of pain occurrence in women with endometriosis (EM).

MATERIALS AND METHODS:

-1195 A/G polymorphism in the promoter region of COX-2 gene was analyzed in 32 EM patients with pain, 28 EM patients without pain, and 29 healthy controls in a Chinese population using a PCR-RFLP assay.

RESULTS:

AA homozygote carriers and A allelic frequencies for -1195 A/G polymorphism in COX-2 gene were significantly increased in EM patients compared with the healthy controls (p < 0.001). In addition, further subgroup analysis revealed that the AA genotype and A allele of the -1195 A/G variant were present at a significantly higher frequency in the severe pain group than those in the mild and moderate pain groups. Compared with the controls, the risk of developing EM was 2.86-fold higher in individuals with -1195 AA containing the haplotype, and the risk of developing pain was 2.33-fold higher in EM patients with -1195 AA containing the haplotype.

CONCLUSIONS:

These findings suggest that the -1195 A/G on the promoter region of COX-2 gene may increase the risk of pain occurrence in EM women, possibly by affecting the rate of gene expression, especially in patients with the pain phenotype.

 

 

Geburtshilfe Frauenheilkd. 2016 Apr;76(4):417-422.

Diagnostics and Therapy for Malignant (Degenerate) Colon Endometriosis – Three Case Reports.

Schutz R1Woziwodzki J2Schweppe KW1.

 

Abstract

in EnglishGerman

Malignant degeneration of colon endometriosis is a very rare event. We report here on three cases. A 48-year-old woman with a 10-year history of endometriosis was treated for a rectal adenocarcinoma, a 61-year-old G1P1, who was operated at the age of 40 years for ovarian endometriosis and again at the age of 53 years for an endometriosis-associated endometroid ovarian carcinoma, presented for therapy for a lymph node recurrence of the ovarian cancer and, secondly, due to a malignantly degenerated rectum-sigmoid colon endometriosis; furthermore a 54-year old woman with a 21-year history of endometriosis was operated for malignant colon endometriosis. The tumour occurred during an adjuvant anti-oestrogen treatment with an aromatase inhibitor following surgical and radiotherapy for breast cancer. In all cases a radical cancer operation was followed by adjuvant chemotherapy and in one case with an additional radiotherapy. In the follow-up periods of 18 months, 2 and 5 years, respectively, all women remained free of recurrences. Although this is not a randomised controlled study due to the rare occurrence of such cases, a radical operation followed by individualised adjuvant therapy appears to be the treatment of choice.

 

 

 

 

J Clin Diagn Res. 2016 Mar;10(3):ED03-4.

Co-existence of Endometriotic Cyst of the Ovary and Arias-Stella Reaction in a Non-Pregnant Woman: Report of a Rare Case.

Harikrishnan V1Esaki M2Srinivasan C3Arockiasamy P4Ethirajan S5.

 

Abstract

Endometriosis is defined as presence of endometrial tissue outside the uterus. It can occur anywhere in the ovary. In the ovary it is usually presented as cyst, termed as endometriotic cyst or Chocolate cyst. Arias-Stella reaction is usually seen in gestational endometrium or in ectopic gestation site and rarely in non-pregnant uterus with hormonal intake. Co-existence of endometriosis and Arias-Stella reaction is very rare. We present a very rare case of endometriotic cyst of the ovary exhibiting Arias -Stella reaction which was seen in of non pregnant patient without any history of hormonal intake.

 

 

J Cell Physiol. 2016 Dec;231(12):2622-7.

Prototype of Multiplex Bead Assay for Quantification of Three Serum Biomarkers for In Vitro Diagnosis of Endometriosis.

Signorile PG1Baldi A1.

 

Abstract

Endometriosis is a very common disease, affecting 10% of women in the reproductive age. To date, a significant delay between onset of the symptoms and definitive diagnosis is caused by the lack of a reliable non-invasive diagnostic test. Recently, the potential value as diagnostic markers for endometriosis of three proteins (Zn-alpha2-glycoprotein, serum albumin, and complement C3 precursor), has been showed. In this article, we have defined the experimental conditions for the development of a multiplex bead array assay for rapid and simultaneous quantification of these three biomarkers in the serum of patients with endometriosis. Finally, pivotal experiments on a small cohort of patients have confirmed the diagnostic value of this assay. J. Cell. Physiol. 231: 2622-2627, 2016. © 2016 Wiley Periodicals, Inc.

 

 

Hum Reprod. 2016 Jul;31(7):1475-82.

A prospective cohort study of endometriosis and subsequent risk of infertility.

Prescott J1Farland LV2Tobias DK3Gaskins AJ4Spiegelman D5Chavarro JE6Rich-Edwards JW7Barbieri RL8Missmer SA9.

 

Abstract

STUDY QUESTION:

Is there a temporal relationship between endometriosis and infertility?

SUMMARY ANSWER:

Endometriosis is associated with a higher risk of subsequent infertility, but only among women age <35 years.

WHAT IS KNOWN ALREADY:

Endometriosis is the most commonly observed gynecologic pathology among infertile women undergoing laparoscopic examination. Whether endometriosis is a cause of infertility or an incidental discovery during the infertility examination is unknown.

STUDY DESIGN, SIZE, DURATION:

This study included data collected from 58 427 married premenopausal female nurses <40 years of age from 1989 to 2005, who are participants of the Nurses’ Health Study II prospective cohort.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Our exposure was laparoscopically confirmed endometriosis. Multivariate Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for infertility risk (defined as attempting to conceive for >12 months) among women with and without endometriosis.

MAIN RESULTS AND THE ROLE OF CHANCE:

We identified 4612 incident cases of infertility due to any cause over 362 219 person-years of follow-up. Compared with women without a history of endometriosis, women with endometriosis had an age-adjusted 2-fold increased risk of incident infertility (HR = 2.12, 95% CI = 1.76-2.56) that attenuated slightly after accounting for parity. The relationship with endometriosis was only observed among women <35 years of age (multivariate HR <35 years = 1.77, 95% CI = 1.46-2.14; multivariate HR 35-39 years = 1.20, 95% CI = 0.94-1.53; P-interaction = 0.008). Risk of primary versus secondary infertility was similar subsequent to endometriosis diagnosis. Among women with primary infertility, 50% became parous after the endometriosis diagnosis, and among all women with endometriosis, 83% were parous by age 40 years.

LIMITATIONS, REASONS FOR CAUTION:

We did not have information on participants’ intentions to conceive, but by restricting the analytic population to married women we increased the likelihood that pregnancies were planned (and therefore infertility would be recognized). Women in our cohort with undiagnosed asymptomatic endometriosiswill be misclassified as unexposed. However, the small proportion of these women are diluted among the >50 000 women accurately classified as endometriosis-free, minimizing the impact of exposure misclassification on the effect estimates.

WIDER IMPLICATIONS OF THE FINDINGS:

This study supports a temporal association between endometriosisand infertility risk. Our prospective analysis indicates a possible detection bias in previous studies, with our findings suggesting that the infertility risk posed by endometriosis is about half the estimates observed in cross-sectional analyses.

 

 

 

Int J Reprod Biomed (Yazd). 2015 Dec;13(12):787-92.

Serum levels of lycopene, beta-carotene, and retinol and their correlation with sperm DNA damage in normospermic and infertile men.

Ghyasvand T1Goodarzi MT2Amiri I3Karimi J1Ghorbani M3.

 

Abstract

BACKGROUND:

Oxidative stress in reproductive system leads to sperm DNA damage and sperm membrane lipid peroxidation and may play an important role in the pathogenesis of male infertility, especially in idiopathic cases. Antioxidants such as carotenoids function against free radical damages.

OBJECTIVE:

The aim of this study was to determine the levels of lycopene, beta-carotene and retinol in serum and their relationship with sperm DNA damage and lipid peroxidation in infertile and normospermic males.

MATERIALS AND METHODS:

Sixty two infertile men and 71 normospermic men participated in this study. Blood and semen samples were collected from all subjects. Sperm DNA damage was measured using TUNEL method. Carotenoids, retinol, and malonedildehyde in serum were also determined.

RESULTS:

DNA fragmentation was higher in infertile group comparing to control group. Serum levels of lycopene, beta-carotene and, vitamin A in infertile men were significantly lower than normospermic men (p< 0.001, =0.005, and =0.003 respectively). While serum MDA was not significantly different between two groups, MDA in seminal plasma of infertile men was significantly higher than control group (p< 0.001).

CONCLUSION:

We concluded that lycopene, beta-carotene, and retinol can reduce sperm DNA fragmentation and lipid peroxidation through their antioxidant effect. Therefore the DNA fragmentation assay and determination of antioxidants factors such as lycopene, beta-carotene and retinol, along with sperm analysis can be useful in diagnosis and treatment of men with idiopathic infertility.

 

 

Int J Reprod Biomed (Yazd). 2016 Jan;14(1):1-8.

(1)H NMR- based metabolomics approaches as non- invasive tools for diagnosis of endometriosis.

Ghazi N1Arjmand M2Akbari Z2Mellati AO3Saheb-Kashaf H4Zamani Z2.

 

Abstract

BACKGROUND:

So far, non-invasive diagnostic approaches such as ultrasound, magnetic resonance imaging, or blood tests do not have sufficient diagnostic power for endometriosis disease. Lack of a non-invasive diagnostic test contributes to the long delay between onset of symptoms and diagnosis of endometriosis.

OBJECTIVE:

The present study focuses on the identification of predictive biomarkers in serum by pattern recognition techniques and uses partial least square discriminant analysis, multi-layer feed forward artificial neural networks (ANNs) and quadratic discriminant analysis (QDA) modeling tools for the early diagnosis of endometriosisin a minimally invasive manner by (1)H- NMR based metabolomics.

MATERIALS AND METHODS:

This prospective cohort study was done in Pasteur Institute, Iran in June 2013. Serum samples of 31 infertile women with endometriosis (stage II and III) who confirmed by diagnostic laparoscopy and 15 normal women were collected and analyzed by nuclear magnetic resonance spectroscopy. The model was built by using partial least square discriminant analysis, QDA, and ANNs to determine classifier metabolites for early prediction risk of disease.

RESULTS:

The levels of 2- methoxyestron, 2-methoxy estradiol, dehydroepiandrostion androstendione, aldosterone, and deoxy corticosterone were enhanced significantly in infertile group. While cholesterol and primary bile acids levels were decreased. QDA model showed significant difference between two study groups. Positive and negative predict value levels obtained about 71% and 78%, respectively. ANNs provided also criteria for detection of endometriosis.

CONCLUSION:

The QDA and ANNs modeling can be used as computational tools in noninvasive diagnose of endometriosis. However, the model designed by QDA methods is more efficient compared to ANNs in diagnosis of endometriosis patients.

 

 

 

Arch Gynecol Obstet. 2016 Aug;294(2):417-22

Functional histology and possible clinical significance of recently discovered telocytes inside the female reproductive system.

Varga I1Urban L2,3Kajanová M2,3Polák Š2.

 

Abstract

PURPOSE:

Key discoveries of recent years comprise detection of telocytes. These cells of connective tissue have extremely long cytoplasmic processes through which they form functionally connected spatial networks. Through their processes they mutually contact and functionally connect also cells of the immune system, nerve fibres and smooth muscle cells. They are located in various parts of the female reproductive system where they can perform specifically significant functions, which are summarized in our literature review.

METHODS:

Literature regarding “telocytes” and “interstitial Cajal-like cells” was reviewed using scientific databases PubMed/Medline, SCOPUS, and Web of Knowledge.

RESULTS:

Among other things telocytes regulate peristaltic muscle movements in the uterine tubes. Their decreased activity, e.g., in inflammatory diseases or endometriosis, causes disorders of a transport function through the uterine tubes resulting in infertility or tubal pregnancy. In the uterine myometrium they are, first, responsible for regulation of muscle contraction (in expelling menstrual blood or in childbirth) and, second, they participate also in immune surveillance during embryo implantation. They likely control also uterine involution post partum. Their function in the vagina has not been elucidated yet, but probably they participate in production of slow contraction waves during sexual intercourse. In the mammary gland their function may be to regulate cellular proliferation and apoptosis, thus they may play a role also in the development and growth of tumours. In the placenta, they may monitor and regulate blood flow through chorionic villi and they participate in aetiopathogenesis of preeclampsia.

CONCLUSION:

However, all above-mentioned functions of telocytes are purely hypothetic and have been published only recently. Therefore, only further research will demonstrate whether this recently discovered cell population will really play a key role in all processes mentioned, or whether it is just an effort of scientists to clarify unknown cause of some diseases in gynaecology and obstetrics. Our literature review is completed by our own original photomicrographs documenting telocytes in various organs of the female reproductive system.

 

 

Fertil Steril. 2016 Aug;106(2):416-22.

Administration of atosiban in patients with endometriosis undergoing frozen-thawed embryo transfer: a prospective, randomized study.

He Y1Wu H1He X1Xing Q1Zhou P1Cao Y1Wei Z2.

 

Abstract

OBJECTIVE:

To examine the effects of atosiban, given before transfer of frozen-thawed embryo to women with endometriosis (EMs).

DESIGN:

A randomized, controlled clinical trial.

SETTING:

University hospital and IVF center.

PATIENT(S):

One hundred twenty women with endometriosis undergoing frozen-thawed embryo transfer were randomly allocated into the atosiban treatment and the control groups. Another 120 women with infertility due to tubal factor were enrolled into a tubal factor group, to compare serum oxytocin (OT) and prostaglandin (PG)F2α levels and uterine contractions with the endometriosis group.

INTERVENTION(S):

In the endometriosis treatment group, a single bolus (6.75 mg, 0.9 mL per vial) of atosiban was administrated before ET.

MAIN OUTCOME MEASURE(S):

Implantation rate and pregnancy rate.

RESULT(S):

Serum OT level (1.89 ± 0.33 vs. 1.66 ± 0.32 ng/L), PGF2α (2.83 ± 0.34 vs. 2.36 ± 0.35 ng/L) level, and uterine contractions (2.5 ± 1.2 vs. 1.8 ± 1.0 waves per minute) in the endometriosis group were all significantly higher than in the tubal factor group. The clinical pregnancy rate per cycle and implantation rate per transfer were 58.3% and 41.0%, respectively, in the atosiban treatment group, significantly higher than in the control group (38.3% and 23.4%, respectively).

CONCLUSION(S):

Women with endometriosis showed higher serum OT level, PGF2α level, and uterine contractions. Atosiban treatment before ET in endometriosis is effective in the priming of the uterus, suitable for embryo implantation. This is the first study to evaluate the effect of atosiban treatment in patients with endometriosis.

 

 

 

J Obstet Gynaecol. 2016 Aug;36(6):800-805.

Fertility rates, course of pregnancy and perinatal outcomes after laparoscopic ureterolysis for deep endometriosis: A long-term follow-up study.

Uccella S1Cromi A1Agosti M2Casarin J1Pinelli C1Marconi N1Bertoli F1Podesta’-Alluvion C1Ghezzi F1.

 

Abstract

We evaluated fertility rates, pregnancy course and maternal/neonatal outcomes following laparoscopic ureterolysis for deep endometriosis. Data about women who underwent laparoscopic excision of ureteral endometriosis were analysed. After exclusion of women who underwent hysterectomy/bilateral adnexectomy at initial surgery, and those lost-to-follow-up or with follow-up <1 year, a total of 61 patients were included. Of them, 36 (59%) wished to conceive after surgery. Twenty women became pregnant: nine (45%) of them after assisted reproductive technologies. Twenty-six pregnancies were observed with four (15.6%) miscarriages. Median gestational week at delivery was 38 weeks + 2 days (range, 33 + 1-41 + 6), with three (13.6%) and two (9%) deliveries before 37 and 34 weeks, respectively. Nine caesarean sections were performed (40.9%). Fertility rates after laparoscopic ureterolysis are comparable to those of other women operated for other forms of deep endometriosis. Apart from a higher risk of caesarean and preterm birth, the course of pregnancy and peripartum outcomes appear encouraging.

 

 

J Surg Case Rep. 2016 May 3;2016(5).

Nonoperative management of an anastomotic leak following rectosigmoid resection and anastomosis for Stage IV endometriosis.

DeStephano CC1Paz-Fumagalli R2Pettit PD2.

 

Abstract

Anastomotic leakage is a dreaded complication of gastrointestinal surgery. The complication is difficult to manage and is associated with prolonged hospitalizations and increased morbidity and mortality. We present the nonsurgical management and the use of a fibrin sealant for an anastomotic leak that followed rectosigmoid resection and anastomosis for Stage IV endometriosis. This approach requires a clinically stable patient who is willing to follow-up over a prolonged period of time until the leak is completely sealed. Tissue sealants can be considered when an air leak or fistulous tract persists despite drainage and antibiotics.

 

 

Acta Inform Med. 2016 Apr;24(2):103-6.

The Significance of MRI Evaluation of the Uterine Junctional Zone in the Early Diagnosis of Adenomyosis.

Sofic A1Husic-Selimovic A2Carovac A1Jahic E1Smailbegovic V3Kupusovic J2.

 

Abstract

GOAL:

The aim of the study is to define the MRI appearance of disorder in the Junctional zone (JZ) in women with adenomyosis compared to those without it, given the importance of the JZ in the regulation of various reproductive events.

MATERIALS AND METHODS:

This was a prospective, comparative and open study. Patients with adenomyosis have been sorted in target group, n = 82, while the control group consisted of patients without adenomyosis, n = 82. All patients, from both groups have undergone a magnetic resonance imaging of the pelvis. Using a software tool for measurement, the thickness of the JZ was measured in T2w sag sequences in all patients from both groups (target and control) n = 164. Patients in the target group type adenomyosis were assessed and categorized either as: diffuse, focal, or Adenomyoma and the results were compared. The presence of endometriosis and myomas in both groups was evaluated and its coexistence with adenomyosis was analyzed as well.

RESULTS:

Of the 82 patients in the target group, 81.7% of the patients had diffuse adenomyosis, while 18.3% had focal type with statistically significant difference (p <0.05). The results of the Mann-Whitney U test showed that p <0.05, implying that there is a statistically significant difference in the thickness of the JZ between the control and target group, therefore patients from the target group with adenomyosis had a statistically significantly thicker junctional zone than the patients in the control group. The JZ in the target group was on average M = 14,3mm, SD = 1.3mm, while the thickness of JZ in the control group without adenomyosis was M = 5,6mm, SD = 1,3. Chi-square shows that p <0.05, implying that there is a statistically significant difference in the number of patients with myomas between the two groups, where the myomas significantly over-represented in the target group with 32,9 % vs.6 %).

CONCLUSION:

MRI is the method of choice for imaging and evaluation of JZ as an important diagnostic marker in the diagnosis of adenomyosis. It is important to recognize this condition as early as possible and distinguish it from other pathologies in order for timely and appropriate treatment.

 

 

Mater Sociomed. 2016 Apr;28(2):91-4.

EFFECT OF PELVIC ENDOMETRIOSIS, ENDOMETRIOMAS AND RECURRENT ENDOMETRIOMAS ON IVF-ET/ICSI OUTCOMES.

Xing W1Lin H2Wu Z2Li Y2Zhang Q2.

 

Abstract

INTRODUCTION:

Endometriosis, the most common gynecological disorder, is a challenging disease observed in 20% – 40% of subfertile women.

MATERIAL AND METHODS:

380 women were divided into four groups. Group A consisted of 176 women with pelvic endometriosis. Group B consisted of 125 women who had previously undergone a laparoscopic endometrioma cystectomy. Group C consisted of 38 women with recurrent endometriomas without aspiration before IVF-ET/ICSI. Group D consisted of 41 women with recurrent endometriomas undergone aspiration before IVF-ET/ICSI.

RESULTS:

Baseline FSH level (8.61 ± 3.42 mIU/mL) and total dose of Gn (2337.15 ± 853.00 IU) in Group A were the lowest (p < 0.05). The number of retrieved oocytes in Group B (7.98 ± 5.05) was significantly fewer than those in Group A and D (p < 0.05). The numbers of MII oocytes in Groups A, C and D were significantly larger than that in Group B. The number of retrieved oocytes, high-quality embryos, implantation and pregnancy rates were similar in Groups C and D.

CONCLUSIONS:

Pelvic endometriosis had a less adverse effect on ovarian reserve than endometrioma. No advantage was found in transvaginal aspiration for recurrent endometriomas before IVF-ET/ICSI.

 

 

Biomed Res Int. 2016;2016:3260952.

Epidemiology of Endometriosis in France: A Large, Nation-Wide Study Based on Hospital Discharge Data.

von Theobald P1Cottenet J2Iacobelli S3Quantin C4.

 

Abstract

We aimed to assess the prevalence of hospitalization for endometriosis in the general population in France and in each French region and to describe temporal trends, rehospitalization rates, and prevalence of the different types of endometriosis. The analyses were carried out on French hospital discharge data and covered the period 2008-2012 and a population of 14,239,197 women of childbearing age. In this population, the prevalence of hospitalization for endometriosis was 0.9%, ranging from 0.4% to 1.6% between regions. Endometriosis affected 1.5% of hospitalized women of childbearing age, ranging from 1.0% to 2.4% between regions. The number of patients hospitalized for endometriosis significantly increased over the study period (p < 0.01). Of these, 4.2% were rehospitalized at least once at one year: ranging from 2.7% to 6.3% between regions. The cumulative rehospitalization rate at 3 years was 6.9%. The types of endometriosis according to the procedures performed were as follows: ovarian (40-50%), peritoneal (20-30%), intestinal (10-20%), and ureteral or bladder (<10%), with significant differences between regions. This is the first detailed epidemiological study of endometriosis in France. Further studies are needed to assess the reasons for the increasing prevalence of endometriosis and for the significant differences in regional prevalence of this disease.

 

 

J Menopausal Med. 2016 Apr;22(1):6-8.

The Relevance of Women’s Diseases, Jun Activation-domain Binding Protein 1 (JAB1) and p27(kip1).

Kim M1Kim TH2Lee HH2.

 

Abstract

The Jun activation-domain binding protein 1 (Jab1) recognize a potential coactivator of activator protein 1 (AP-1) such as c-fos, c-jun transcription factor and the fifth subunit of the COP9 signalosome complex. Also, Jab1 activate the c-jun gene resulted cell proliferation. Not only a powerful tumor suppressor but also regulator of apoptosis negative cdk inhibitor p27(kip1) are involved in the cell cycle. This is Jab1 and p27(kip1) interact with each other, Jab1 accelerate p27(kip1) from nuclear to cytoplasm through ubiquitin/proteasome pathway. However, information about the relationship between Jab1 and p27(kip1) is not known much. Taken together, the results of this study identify function and structure of Jab1 and p27(kip1) were described in a recent article on the basis of relevant. Besides Jab1 and p27(kip1) will organize the relationship between the disease and women.

 

 

 

Int J Surg Case Rep. 2016;23:163-8.

Small bowel obstruction due to an endometriotic ileal stricture with associated appendiceal endometriosis: A case report and systematic review of the literature.

Sali PA1Yadav KS2Desai GS3Bhole BP4George A5Parikh SS6Mehta HS7.

 

Abstract

INTRODUCTION:

Endometriosis is defined as the presence of functional ectopic endometrial tissue outside the uterine cavity. It rarely involves the small bowel and obstruction due to the same is highly uncommon. Preoperative diagnosis is difficult based on clinical and radiological studies. Diagnosis can be confirmed only on histopathological examination of the surgically resected specimen.

PRESENTATION OF CASE:

A 44 years old lady presented with repeated episodes of abdominal pain, non bilious vomiting and diarrhea. She also gave history of abdominal pain during every menstruation. She had diffuse abdominal tenderness and the computed tomography showed a concentric infective/inflammatory thickening of the distal ileum. Colonoscopy confirmed a tight distal ileal stricture After a failed trial of conservative management, she underwent a laparoscopic right hemicolectomy. The histopathological examination revealed multiple endometriotic foci in the ileum and the appendix.

DISCUSSION:

Ileal endometriosis presenting as obstruction is uncommon and very few cases have been reported thus far. The symptoms are usually cyclical but may later become continuous with the progression of the disease. Preoperative diagnostic dilemma is due to the clinical and the radiological similarities to inflammatory, infective and irritable bowel diseases.

CONCLUSION:

Ours is probably the first case of small bowel obstruction due to ileal and appendiceal endometriosis that was managed with laparoscopic right hemicolectomy. We highlight the preoperative diagnostic dilemma and the progression of the cyclical symptoms. Thus, endometriosis must be considered in cases of small bowel obstruction in women in the reproductive age group as a rare cause.

 

 

Obstet Gynecol. 2016 Jun;127(6):1045-53

Prevalence of Endometriosis During Abdominal or Laparoscopic Hysterectomy for Chronic Pelvic Pain.

Mowers EL1Lim CSSkinner BMahnert NKamdar NMorgan DMAs-Sanie S.

 

Abstract

OBJECTIVE:

To estimate the prevalence of surgically confirmed endometriosis in women undergoing laparoscopic or abdominal hysterectomy, including those with and without preoperative indications of chronic pelvic pain or endometriosis, and to describe characteristics and operative findings associated with surgically confirmed endometriosis in women undergoing hysterectomy for chronic pelvic pain.

METHODS:

A retrospective cohort study was performed with 9,622 women who underwent laparoscopic or abdominal hysterectomy for benign indications in the Michigan Surgical Quality Collaborative from January 1, 2013, to July 2, 2014. The prevalence of surgically confirmed endometriosis, determined by review of the operative report and surgical pathology, was calculated for the entire cohort and for subgroups of women with and without chronic pelvic pain or endometriosis. Multivariate logistic regression models were used to identify characteristics associated with surgically confirmed endometriosis at the time of hysterectomy among women with chronic pelvic pain.

RESULTS:

Of the 9,622 hysterectomies available for analysis during the study period, 15.2% (n=1,465) had endometriosis at the time of hysterectomy. Among the 3,768 women with a preoperative indication of chronic pelvic pain, fewer than one in four had endometriosis (806/3,768 [21.4%]). Even among those with preoperative indication of endometriosis, many women did not actually have endometriosis at the time of hysterectomy (527/1,232 [42.8%]). The rate of unexpected endometriosis in women without a preoperative indication of chronic pelvic pain or endometriosis was 8.0% (434/5,457). Among women with a preoperative indication of chronic pelvic pain (n=3,786), multivariate analysis showed endometriosis was more common in women of younger age, white race, lower body mass index, and those who failed another treatment previously. Among those with pelvic pain, oophorectomy was more commonly performed in women with surgically confirmed endometriosis than those without (47.4% compared with 33.3%, P<.001).

CONCLUSION:

Fewer than 25% of women undergoing laparoscopic or abdominal hysterectomy for chronic pelvic pain have endometriosis at the time of surgery.

 

 

J Med Internet Res. 2016 May 9;18(5):e109.

Therapeutic Affordances of Online Support Group Use in Women With Endometriosis.

Shoebotham A1Coulson NS.

 

Abstract

BACKGROUND:

The Internet has provided women living with endometriosis new opportunities to seek support online. Online support groups may provide a range of therapeutic affordances that may benefit these women.

OBJECTIVE:

To examine the presence of therapeutic affordances as perceived by women who use endometriosisonline support groups.

METHODS:

Sixty-nine women (aged 19-50 years, mean 34.2 years; 65.2% (45/69) United Kingdom, 21.7% (15/69) United States) participated in a Web-based interview exploring online support group use. Participants had been using online support groups for an average of 2 years and 4 months (range = 1 month to 14 years, 9 months). Responses were analyzed using inductive thematic analysis.

RESULTS:

The analysis revealed 4 therapeutic affordances related to online support group use: (1) “connection,” that is, the ability to connect in order to support each other, exchange advice, and to try to overcome feelings of loneliness; (2) “exploration,” that is, the ability to look for information, learn, and bolster their knowledge; (3) “narration,” that is, the ability to share their experiences, as well as read about the experiences of others; and (4) “self-presentation,” that is, the ability to manage how they present themselves online. The associated outcomes of use were predominantly positive, such as reassurance and improved coping. However, a number of negative aspects were revealed including the following: concerns about the accuracy of information, arguments between members, overreliance on the group, becoming upset by negative experiences or good news items, and confidentiality of personal information.

CONCLUSIONS:

Our findings support the previously proposed SCENA (Self-presentation, Connection, Exploration, Narration, and Adaptation) model and reveal a range of positive aspects that may benefit members, particularly in relation to reassurance and coping. However, negative aspects need to be addressed to maximize the potential benefit of support groups. Some of these can be addressed relatively easily through making privacy policies clearer, including health professionals to moderate content, and structuring forums to encourage the sharing of positive stories.

 

 

Gynecol Obstet Invest. 2016;81(5):430-5.

CA125 and HE4: Measurement Tools for Ovarian Cancer.

Zhao T1Hu W.

 

Abstract

AIMS:

This study aimed to examine the clinical significance of carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) serum levels in combination for ovarian cancer detection in patients.

METHODS:

In total, 75 patients with ovarian cancer, 86 patients with benign ovarian tumors, 75 patients with endometriosis and 34 healthy women (as a control group) were selected from January 2012 to July 2015 at Anhui province hospitals. The sensitivity and specificity of detection of CA125, HE4 and combined CA125 + HE4 in serum were analyzed for each group.

RESULTS:

HE4 and CA125 serum levels in the ovarian cancer group were higher than those in the other 3 groups (p < 0.001). The sensitivity of CA125 was higher than that of HE4 (88.2 vs. 54.7%, respectively), whereas the specificity of HE4 was higher than that of CA125 (97.9 vs. 67.4%, respectively). In contrast, the sensitivity and specificity of HE4 combined with CA125 were 82.7 and 91.4%, respectively. The receiver operating characteristic-area under the curve values of HE4, CA125 and HE4 + CA125 were 0.889, 0.893 and 0.925, respectively.

CONCLUSIONS:

Combined detection of CA125 with HE4 can improve the sensitivity and specificity of ovarian cancer diagnosis and has certain clinical significance that can guide treatment planning.

 

 

Clin Exp Pharmacol Physiol. 2016 Aug;43(8):769-76.

Cytoprotective effects of endothelin-1 on mesenchymal stem cells: an in vitro study.

Pourjafar M1Saidijam M1Mansouri K2Malih S1Ranjbar Nejad T1Shabab N1Najafi R1,3.

 

Abstract

Stem cell-based therapies is a promising approach for regenerative therapy in various diseases. Some obstacles remain to be solved before clinical application of the cell therapy is realized, including increasing the survival of transplanted stem cells, reducing loss of transplanted cells, and maintaining adequate vascular supply. Recently, stem cell preconditioning with chemical and pharmacological agents has been shown to increase therapeutic efficacy. The present study investigated the effect of endothelin-1 (ET-1) on survival, angiogenesis, and migration of mesenchymal stem cells (MSCs), in vitro. MSCs were treated with various concentrations of ET-1 and the expression of cyclooxygenase-2 (COX-2), hypoxia-inducible factor-1 (HIF-1), C-X-C chemokine receptor type 4 (CXCR4), C-C chemokine receptor type 2 (CCR2), vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), angiopoietin-4 (Ang-4) and matrix metalloproteinase-2 (MMP-2) were examined. Caspase 3 activity and prostaglandin E2 (PGE2) were determined by ELISA assay. MSCs migration and tube formation potential were assessed using scratch test and three dimensional vessel formation assay. ET-1 enhanced the MSCs viability. In ET-1- treated MSCs, expression of COX-2, HIF-1, CXCR4, CCR2, VEGF, Ang-2, Ang-4 and MMP-2 were increased compared to control groups. Elevation of all these genes were reversed by celecoxib (50 μmol/L), a selective COX-2 inhibitor. PGE2 generation, MSCs migration and tube formation were enhanced by ET-1 conditioning, whereas caspase-3 activity was reduced in these cells, compared to the control group. The results presented here reveal that preconditioning of MSCs with ET-1 has strong cytoprotective effects through activation of survival signalling molecules and trophic factors.

 

 

Reproduction. 2016 Sep;152(3):R63-78.

Endometriosis: where are we and where are we going?

Greene AD1Lang SA2Kendziorski JA2Sroga-Rios JM1Herzog TJ3Burns KA4.

 

Abstract

Endometriosis currently affects ~5.5 million reproductive-aged women in the U.S. with symptoms such as painful periods (dysmenorrhea), chronic pelvic pain, pain with intercourse (dyspareunia), and infertility. It is defined as the presence of endometrial tissue outside the uterine cavity and is found predominately attached to sites within the peritoneal cavity. Diagnosis for endometriosis is solely made through surgery as no consistent biomarkers for disease diagnosis exist. There is no cure for endometriosis and treatments only target symptoms and not the underlying mechanism(s) of disease. The nature of individual predisposing factors or inherent defects in the endometrium, immune system, and/or peritoneal cavity of women with endometriosis remains unclear. The literature over the last 5 years (2010-2015) has advanced our critical knowledge related to hormones, hormone receptors, immune dysregulation, hormonal treatments, and the transformation of endometriosis to ovarian cancer. In this review, we cover the aforementioned topics with the goal of providing the reader an overview and related references for further study to highlight the progress made in endometriosis research, while concluding with critical areas of endometriosis research that are urgently needed.

 

 

Hum Reprod. 2016 Jul;31(7):1515-21.

Personality in women with endometriosis: temperament and character dimensions and pelvic pain.

Facchin F1Barbara G2Saita E3Erzegovesi S4Martoni RM4Vercellini P5.

 

Abstract

STUDY QUESTION:

Is pelvic pain due to endometriosis associated with temperament and character dimensions?

SUMMARY ANSWER:

Women with endometriosis and pelvic pain do not clearly exhibit a specific personality profile; however, personality is associated with pelvic pain perception.

WHAT IS KNOWN ALREADY:

There is research evidence suggesting that endometriosis patients with pelvic pain are more likely to present psychological disruption. Little is known about the association between subjective factors, such as personality traits, and pelvic pain.

STUDY DESIGN, SIZE, DURATION:

This cross-sectional study (N = 133) is part of a larger research on the association between endometriosis and several psychological variables carried out between 2012 and 2014.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS:

The participants were 82 endometriosis patients and 51 healthy controls. Endometriosis patients indicated on a dichotomous scale (yes/no) whether they were suffering from pelvic pain and were divided in two study groups: painful endometriosis group (N = 58) and pain-free endometriosis group (N = 24). The severity of pelvic pain (chronic pelvic pain, dysmenorrhoea, dyspareunia, and dyschezia) was rated on a 0-10 point numerical rating scale. All participants completed a 240-item psychometric test (TCI-R) evaluating personality in terms of temperament and character dimensions.

MAIN RESULTS AND THE ROLE OF CHANCE:

Women with painful endometriosis had lower novelty seeking compared with the control group (P = 0.017) and higher harm avoidance (P = 0.007) and lower exploratory excitability (P = 0.034) and responsibility (P = 0.027) compared with the pain-free endometriosis group, as well as higher fatigability compared with the pain-free endometriosis group (P = 0.001) and the control group (P = 0.032). Higher harm avoidance (B = 0.081; P = 0.002) and lower self-directedness (B = -0.053; P = 0.015) were associated with a greater severity of chronic pelvic pain.

LIMITATIONS, REASONS FOR CAUTION:

These study findings should be taken cautiously for several methodological reasons such as small sample size, differences in group sizes and cultural homogeneity. More research is needed to further investigate the association between personality and pelvic pain related to endometriosis.

WIDER IMPLICATIONS OF THE FINDINGS:

Our findings suggest new avenues for future research and treatment of endometriosis. The association between the severity of chronic pelvic pain and personality may help clarify the lack of a direct correlation between pain severity and the type and stage of endometriosis, as well as the inconsistencies in patients’ response to medical and/or surgical treatment. Therapeutic strategies should be specifically targeted on individual women and involve an integrated approach to the treatment of chronic pelvic pain related to endometriosis.

 

 

J Assist Reprod Genet. 2016 Aug;33(8):1105-13.

Epigenetic alterations of CYP19A1 gene in Cumulus cells and its relevance to infertility in endometriosis.

Hosseini E1Mehraein F2Shahhoseini M3Karimian L4Nikmard F1Ashrafi M5Afsharian P3Aflatoonian R6.

 

Abstract

PURPOSE:

The purpose of the present study was to investigate the epigenetic mechanisms responsible for the aberrant aromatase expression (CYP19A1) in Cumulus Cells (CCs) of infertile endometriosis patients.

METHOD:

Cumulus cells were obtained from 24 infertile patients with and without endometriosis who underwent ovarian stimulation for intracytoplasmic sperm injection. Expression of CYP19A1 gene was quantified using Reverse Transcription Q-PCR. DNA methylation, histone modifications, and binding of Estrogen Receptor, ERβ to regulatory DNA sequences of CYP19A1 gene were evaluated by Chromatin ImmunoPrecipitation (ChIP) assay.

RESULTS:

CYP19A1 gene expression in CCs of endometriosis patients was significantly lower than the control group (P = 0.04). Higher incorporation of MeCP2 (as a marker of DNA methylation) on PII and PI.4 promoters, and hypoacetylation at H3K9 in PII and hypermethylation at H3K9 in PI.4 were observed in CYP19A1 gene in endometriosis patients (P < 0.05). Moreover, a decreased level of ERβ binding to PII and an increased level of its binding to PI.3 and PI.4 promoters of CYP19A1 were observed in endometriosis patients when compared to control.

CONCLUSION:

Significant reduction of CYP19A1 gene expression in CCs of endometriosis patients may be the result of epigenetic alterations in its regulatory regions, either by DNA methylation or histone modifications. These epigenetic changes along with differential binding of ERβ (as a transcription factor) in CYP19A1 promoters may impair follicular steroidogenesis, leading to poor Oocyte and embryo condition in endometriosis patients.

 

 

 

Abdom Radiol (NY). 2016 Dec;41(12):2476-2483.

Clear cell carcinoma of the ovary: comparison of MR findings of histological subtypes.

Kato H1Hatano Y2Makino H3Furui T3Morishige KI3Matsuo M4.

 

Abstract

PURPOSE:

To retrospectively compare the MR findings of histological subtypes of clear cell carcinomas (CCCs) of the ovary.

MATERIALS AND METHODS:

This single-center retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. Between April 2005 and August 2015, we found 51 consecutive patients with histopathologically proven CCCs. Among them, 44 CCCs in 37 patients who underwent preoperative MR imaging were included. CCCs were pathologically divided into three subgroups: (1) four clear cell adenofibroma-associated CCCs, (2) 21 endometriosis-associated CCCs, and (3) 19 indeterminate CCCs. The statistical tests were used to compare the frequency of qualitative assessments and value of quantitative measurements among the histological subtypes.

RESULTS:

On T2-weighted images, hypointense areas within solid components were more frequently observed in clear cell adenofibroma-associated CCCs [3/4 (75%)] than in the remaining CCCs [1/40 (3%)] (p < 0.01), and the signal intensity ratios (SIRs) of solid components were significantly lower in clear cell adenofibroma-associated CCCs (0.27 ± 0.13) than in the remaining CCCs (0.61 ± 0.18) (p < 0.01). On T1-weighted images, hyperintensities of cystic components were more frequently observed in the endometriosis-associated CCCs [17/21 (81%)] than in the remaining CCCs [5/20 (25%)] (p < 0.01), and the SIRs of cystic components were significantly higher in endometriosis-associated CCCs (2.99 ± 1.51) than in the remaining CCCs (1.82 ± 1.10) (p < 0.01).

CONCLUSION:

MR features may help differentiate between adenofibroma-associated and endometriosis-associated CCC.

 

 

Arch Gynecol Obstet. 2016 Oct;294(4):771-8.

Impact of endometriosis on surgical outcomes and complications of total laparoscopic hysterectomy.

Uccella S1Marconi N2Casarin J2Ceccaroni M3Boni L4Sturla D2Serati M2Carollo S2Podesta’ Alluvion C2Ghezzi F2.

 

Abstract

PURPOSE:

Total laparoscopic hysterectomy (TLH) in the case of endometriosis may be extremely challenging. Our aim has been to analyze perioperative details and complications of TLH in women with vs. women without endometriosis.

METHODS:

Consecutive women who underwent TLH for endometriosis (endometriosis group) were compared with consecutive patients who had TLH for other conditions (controls) in terms of perioperative outcomes. Patients in the endometriosis group were analyzed, according to the severity of the disease.

RESULTS:

One-hundred and twelve women in the endometriosis group, 29 (25.9 %) with minimal-mild, and 83 (74.1 %) with moderate-severe stage disease (rAFS score), respectively, were compared with 572 controls. Conversion rate was 0.8 vs. 0.5 % (P = 0.51), and median operative time was 75 vs. 55 min (pxxx = x) in the endometriosis group vs.

CONTROLS:

Intraoperative complications were similar between groups (P = 0.56). Postoperative complications occurred in 10 (12.3 %) women in the endometriosis group vs. 12 (3.3 %) among the controls (P = 0.002). The severity of complications according to Clavien-Dindo classification system was higher in the endometriosis group (Clavien-Dindo >2: 7.5 vs. 1.9 %). The risk of organ lesions, urinary lesions, postoperative complications, and severe adverse events was significantly higher in women with moderate-severe endometriosis vs.

CONTROLS:

No differences between patients with minimal-mild endometriosis and controls were found.

CONCLUSION(S):

TLH in the case of endometriosis is associated with longer operative time and an almost fourfold increase in the risk and severity of complications compared with controls. In particular, the adjunctive risk of adverse events is specific for moderate/severe-stage disease but not for minimal/mild endometriosis.

 

 

Acta Cir Bras. 2016 Apr;31(4):227-34.

Evaluation of peritoneal endometriosis treatment using intralesional acetylsalicylic acid injection in rabbits.

Saad-Hossne R1Barretto AB2Siqueira JM2Denadai R2.

 

Abstract

PURPOSE:

To investigate the efficacy of intralesional 20% aspirin injection for treatment of experimental peritoneal endometriosis.

METHODS:

Peritoneal endometriosis was experimentally induced in forty adult nulligravid female rabbits. On day 30 post-endometriosis induction, rabbits were randomly divided to assess early (10 days) and late (20 days) effects of intralesional injection of physiological saline solution (control groups) in comparison to intralesional injection of 20% bicarbonate aspirin solution (experimental groups) as follows: control group 1 (10 days, n=10); control group 2 (20 days, n=10); experimental group 3 (10 days, n=10); experimental group 4 (20 days, n=10). Resected tissues, including endometriosis foci, were qualitatively (general morphology and signs of inflammatory cells infiltrate, necrosis and apoptosis) and quantitatively (remaining endometriosis area) assessed by histopathological analysis.

RESULTS:

Extensive necrosis, hemorrhage, apoptosis, and fibrosis were observed in the experimental groups 3 and 4. Groups 1 and 2 presented typical endometrial tissue cysts, respectively. Groups 3 and 4 showed sparse endometrial tissue foci and no endometrial tissue, respectively. Quantitative analysis revealed that aspirin-treated groups 3 and 4 had significantly (p<0.05) smaller remaining endometriosis area, compared to control groups 1 and 2.

CONCLUSION:

Intralesional 20% aspirin injection caused total destruction of peritoneal endometriosis foci in rabbits.

 

 

Exp Ther Med. 2016 May;11(5):1633-1646.

Association between glutathione S-transferase M1/T1 gene polymorphisms and susceptibility to endometriosis: A systematic review and meta-analysis.

Xin X1Jin Z1Gu H2Li Y1Wu T1Hua T1Wang H1.

 

Abstract

Endometriosis is a polygenic/multifactorial disease caused by interactions between multiple genes and the environment. Findings from studies evaluating the association between the glutathione S-transferase (GST) M1/T1 null genotype and susceptibility to endometriosis are inconsistent. This meta-analysis updated and reevaluated the possible associations between GSTM1GSTT1 and combined GSTM1/GSTT1 (null genotype versus wild-type) gene polymorphisms and susceptibility to endometriosis. The PubMed, Embase and Chinese BioMedical Literature databases and Google Scholar were searched for case-control genetic association studies on GSTM1/GSTT1 (null genotype versus wild-type) gene polymorphisms and endometriosis in comparison with non-endometriosis or healthy controls. Fixed-effect and random-effect meta-analytical techniques were conducted for the outcome measure and subgroup analyses. The meta-analysis demonstrated significant associations between the GSTM1[odds ratio (OR)=1.56; 95% confidence interval (CI): 1.25-1.95; P<0.0001), GSTT1 (OR=1.31; 95% CI: 1.02-1.68; P=0.037) and GSTM1/GSTT1 (OR=1.68; 95% CI: 1.29-2.17; P<0.0001) null genotypes and increased risk for endometriosis. The results suggest that the GSTM1GSTT1, and combined GSTM1/GSTT1 null genotypes increase susceptibility to endometriosis. Additional well-designed studies and precise analyses are warranted to confirm these findings.

 

 

Eur J Gynaecol Oncol. 2016;37(2):216-20.

Accuracy of intra-operative frozen section and its role in the diagnostic evaluation of ovarian tumors.

Abudukadeer AAzam SZunong BMutailipu AZHuijun BQun L.

 

Abstract

OBJECTIVE:

This retrospective study was undertaken to evaluate the accuracy and role of intra-operative frozen section in the diagnosis of ovarian tumors.

MATERIALS AND METHODS:

Retrospective study of 804 ovarian frozen section results between June 2010 and June 2014 was examined to determine the accuracy of frozen section diagnosis. The intra-operative frozen section diagnosis was compared with the permanent (paraffin) section and the overall accuracy, sensitivity, specificity, and positive and negative predictive values of the frozen section were studied.

RESULTS:

The overall accuracy to determine the status of malignancy was 92.6%. There were 38 (7.4%) false negative and no false positive frozen section diagnoses.The sensitivity, specificity, and positive predictive and negative predictive values for benign ovarian tumors were 100.0%, 97.0%, 91.3%, and 100.0%, respectively; for borderline tumors they were 64.3%, 97.0%, 91.5%, and 94.0%, respectively, and for malignant tumors they were 90.0%, 100.0%, 100.0%, and 85.5%, respectively.

CONCLUSION:

This study concluded that frozen section appears to be an adequate technique for the histopathological diagnosis of ovarian tumors, with some limitations observed among borderline and mucinous tumors.

 

 

BJOG. 2016 Oct;123(11):1761-8.

Diagnostic accuracy of cancer antigen 125 for endometriosis: a systematic review and meta-analysis.

Hirsch M1Duffy J2,3Davis CJ4Nieves Plana M5,6Khan KS4International Collaboration to Harmonise Outcomes and Measures for Endometriosis.

 

Abstract

BACKGROUND:

The development of a non-invasive and accurate diagnostic biomarker for endometriosis is urgently needed.

OBJECTIVE:

Evaluate the diagnostic accuracy of serum cancer antigen 125 (CA 125) for endometriosis.

SEARCH STRATEGY:

We searched EMBASE, MEDLINE, and Web of Science from inception to January 2016.

SELECTION CRITERIA:

Diagnostic accuracy studies of serum CA 125 (index test) for histologically confirmed endometriosis (reference standard) were included.

DATA COLLECTION AND ANALYSIS:

Two authors independently selected trials, extracted study characteristics and data. Methodological quality was assessed using Quality Assessment of Comparative Diagnostic Accuracy Studies (QUADAS-2) checklist.

MAIN RESULTS:

Twenty-two studies (16 cohort, six case-control), 3626 participants, were identified. Bivariate hierarchical models were used to pool accuracy data of 14 studies (2920 participants) using CA 125 ≥ 30 units/ml. Pooled specificity was 93% (95% CI 89-95%) and sensitivity 52% (95% CI 38-66%). CA 125 was significantly more sensitive for the diagnosis of moderate or severe endometriosis compared with minimal disease (63%, 95% CI 47-77% versus 24%, 95%CI 19-32%, P-value = 0.001).

CONCLUSIONS:

CA 125 performs well as a rule-in test facilitating expedited diagnosis and ensuring investigation and treatment can be confidently tailored for the management of endometriosis. Unfortunately, a negative test, CA 125 < 30 units/ml, is unable to rule out endometriosis.

TWEETABLE ABSTRACT:

Blood test CA 125: a rule-in test for the diagnosis of women presenting with symptoms of endometriosis.

 

 

Am Fam Physician. 2016 Apr 15;93(8):676-81.

Diagnosis and Management of Adnexal Masses.

Biggs WS1Marks ST1.

 

Abstract

Adnexal masses can have gynecologic or nongynecologic etiologies, ranging from normal luteal cysts to ovarian cancer to bowel abscesses. Women who report abdominal or pelvic pain, increased abdominal size or bloating, difficulty eating, or rapid satiety that occurs more than 12 times per month in less than a year should be evaluated for ovarian cancer. Pelvic examination has low sensitivity for detecting an adnexal mass; negative pelvic examination findings in a symptomatic woman should not deter further workup. Ectopic pregnancy must be ruled out in women of reproductive age. A cancer antigen 125 (CA 125) test may assist in the evaluation of an adnexal mass in appropriate patients. CA 125 levels are elevated in conditions other than ovarian cancer. Because substantial overlap in CA 125 levels between pre- and postmenopausal women may occur, this level alone is not recommended for differentiating between a benign and a malignant adnexal mass. Transvaginal ultrasonography is the first choice for imaging of an adnexal mass. Large mass size, complexity, projections, septation, irregularity, or bilaterality may indicate cancer. If disease is suspected outside of the ovary, computed tomography may be indicated; magnetic resonance imaging may better show malignant characteristics in the ovary. Serial ultrasonography and periodic measurement of CA 125 levels may help in differentiating between benign or potentially malignant adnexal masses. If an adnexal mass larger than 6 cm is found on ultrasonography, or if findings persist longer than 12 weeks, referral to a gynecologist or gynecologic oncologist is indicated.

 

 

Endocrinology. 2016 Jul;157(7):2870-82

High-Fat Diet Promotion of Endometriosis in an Immunocompetent Mouse Model is Associated With Altered Peripheral and Ectopic Lesion Redox and Inflammatory Status.

Heard ME1Melnyk SB1Simmen FA1Yang Y1Pabona JM1Simmen RC1.

 

Abstract

Endometriosis is a benign gynecological condition that causes considerable morbidity due to associated infertility, debilitating pelvic pain and inflammatory dysfunctions. Diet is a highly modifiable risk factor for many chronic diseases, but its contribution to endometriosis has not been extensively investigated, due partly to the paradoxical inverse association between obesity and disease incidence. Nevertheless, chronic exposure to dietary high-fat intake has been linked to greater systemic inflammation and oxidative stress, both features of women with endometriosis. Here, we evaluated the effects of a high-fat diet (HFD) (45% fat kcal) on endometriosis progression using an immunocompetent mouse model where ectopic lesion incidence was induced in wild-type recipients by ip administration of endometrial fragments from transcription factor Krüppel-like factor 9-null donor mice. We show that HFD significantly increased ectopic lesion numbers in recipient mice with no significant weight gain and modifications in systemic ovarian steroid hormone and insulin levels, relative to control diet-fed (17% fat kcal) mice. HFD promotion of lesion establishment was associated with reductions in stromal estrogen receptor 1 isoform and progesterone receptor expression, increased F4/80-positive macrophage infiltration, higher stromal but not glandular epithelial proliferation, and enhanced expression of proinflammatory and prooxidative stress pathway genes. Lesion-bearing HFD-fed mice also displayed higher peritoneal fluid TNFα and elevated local and systemic redox status than control diet-fed counterparts. Our results suggest that HFD intake exacerbates endometriosisoutcome in the absence of ovarian dysfunction and insulin resistance in mice and warrants further consideration with respect to clinical management of endometriosis progression and recurrence in nonobese patients.

 

 

Minerva Ginecol. 2017 Feb;69(1):100-107.

Ovarian endometriomas in adolescents often represent active angiogenic disease requiring early diagnosis and careful management.

Benagiano G1Bianchi P2Brosens I3.

 

Abstract

As of today, there is no proof that the ovarian endometrioma in an adolescent represents a progressive condition, although evidence is accumulating that active management of this phenotype of endometriosis is warranted. Indeed, although symptoms will often start at a young age, even before menarche, a major delay between their onset and final diagnosis seems almost unavoidable, risking serious damage and impairment of future fertility. Published series of adolescent endometriosis show a relatively frequent presence of endometrioma and a possible rapid progress; furthermore, severity does not seem directly correlated to the degree of pain. Following active management, reported risk of recurrence is high, estimated as between more than 20% at 2 years and 40-50% at 5 years. Unfortunately, no biomarkers of recurrence exist and therefore targeted interventions are impossible. Among factors favoring recurrence, neoangiogenesis and adhesion formation may play an important role. The endometrioma produces a detrimental effect on ovarian function through a number of cellular and molecular features of its bed: in the superficial implant hormonal response in the stromal vessels leads to recurrent bleeding, whereas in the deeper tissue the presence of endometrial glands is associated with smooth muscle metaplasia of the surrounding tissue. Fortunately, the availability of non-invasive imaging techniques and of minimally invasive endoscopic techniques enables today careful investigation and successful management. In conclusion, notwithstanding the existing large gaps in our understanding of the pathogenesis of the ovarian endometrioma, present knowledge suggests that in adolescent girls they often represent a progressive condition necessitating early, active management.

 

 

 

Arch Gynecol Obstet. 2016 Oct;294(4):779-83.

Risk factors for ectopic pregnancy in the Taiwanese population: a retrospective observational study.

Hwang A1Chou L2Islam MM3Li YC3Syed-Abdul S4,5.

 

Abstract

OBJECTIVE:

The aim of this study is to explore the risk factors for ectopic pregnancy (EP) in the Taiwanese population and to identify any unknown risk factors for EP that could assist awareness and diagnosis.

METHODS:

This retrospective case-control study utilizes Taiwan’s National Health Insurance Research Database (NHIRD). Analysis was conducted with a one million sample database representative of the country’s population. The case group comprised of 6637 individuals in the database that coded for EP using the ICD-9 classification system from January 2003 to December 2011. The control group comprised of 13,270 females matched by age that were never diagnosed with EP during the study period.

RESULTS:

This study provides an analysis of the risk factors of EP utilizing NHIRD. Among the 6637 people diagnosed with EP, logistic regression with age adjustment showed that the highest risk factor was endometriosis(OR = 8.84, CI 5.13-15.23), followed by polycystic ovary (OR = 7.74, CI 3.37-17.79) and benign neoplasm of the ovary (6.01, CI 2.18-16.54). All odds ratios were determined to be statistically significant at p < 0.001.

CONCLUSION:

This study has identified the diagnosis of endometriosis and polycystic ovaries as the two largest risk factors for EP in Taiwan, and has also newly identified benign neoplasm of ovary and uterine leiomyoma as risk factors for EP.

 

 

Ann Vasc Surg. 2016 Jul;34:135-43.

The Prevalence of Ovarian Varices in Patients with Endometriosis.

Pacheco KG1Fortes de Oliveira MR2.

 

Abstract

BACKGROUND:

To study the possible association between endometriosis and ovarian varices. These diseases manifest with similar symptomatologies and the hormone estradiol is implicated in both.

METHODS:

The sample consisted of 48 female patients between the ages of 18 and 50 years old. There were 25 patients who had been diagnosed with endometriosis. Fifteen had been confirmed by surgery and histopathology, and 10 by nuclear magnetic resonance. There were also 23 patients without endometriosis who were considered to be the control group. The diagnosis of ovarian varicose veins were made through ultrasound system with endovaginal transducer of 4 to 8 MHz. This study was conducted from May 2013 to September 2014. The researchers attempted to identify the anechoic, circular, linear, and non-pulsatile structures in the broad ligament of the uterus. Varices with dilation of equal to or greater than 5 mm in the longitudinal cut, with tortuous veins with reflux in the adnexal region.

RESULTS:

The prevalence of ovarian varices in patients with endometriosis was 80%, whereas the control group was only 26.1%. The elevated percentage of ovarian varices in patients with endometriosis is highly significant, with a difference of 53.9% and 95% confidence interval of 30%-78%. The criterion for the determination of significance that we adopted was the level of 5%. The statistical analysis was processed using the statistical software SAS system, version 6.11 (SAS Institute, Inc., Cary, North Carolina).

CONCLUSIONS:

Our results suggest that ovarian varices may play a very important role in the physiopathology of endometriosis. Ovarian varices may evolve with oxidative stress in the function of the ovary, provoking an imbalance in its genetic, hormonal, and immunologic aspects and provoking the chronic inflammatory process particular to endometriosis.

 

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