J Long Term Eff Med Implants. 2015;25(3):245-52

Economic Impact of the Use of an Absorbable Adhesion Barrier in Preventing Adhesions Following Open Gynecologic Surgeries.

Roy S¹, Carlton R², Weisberg M¹, Clark R², Migliaccio-Walle K³, Chapa H⁴.

 

Abstract

We used an economic model to assess the impact of using the GYNECARE INTERCEED absorbable adhesion barrier for reducing the incidence of postoperative adhesions in open surgical gynecologic procedures. Caesarean section surgery, hysterectomy, myomectomy, ovarian surgery, tubal surgery, and endometriosis surgery were modeled with and without the use of GYNECARE INTERCEED absorbable adhesion barrier. Incremental GYNECARE INTERCEED absorbable adhesion barrier material costs, medical costs arising from complications, and adhesion-related readmissions were considered. GYNECARE INTERCEED absorbable adhesion barrier use was assumed in 75% of all procedures. The economic impact was reported during a 3-year period from a United States hospital perspective. Assuming 100 gynecologic surgeries of each type and an average of one GYNECARE INTERCEED absorbable adhesion barrier sheet per surgery, a net savings of $540,823 with GYNECARE INTERCEED absorbable adhesion barrier during 3 years is estimated. In addition, GYNECARE INTERCEED absorbable adhesion barrier use resulted in 62 fewer cases of patients developing adhesions. Although the use of GYNECARE INTERCEED absorbable adhesion barrier added $137,250 in material costs, this was completely offset by the reduction in length of stay ($178,766 savings), fewer adhesion-related readmissions ($458,220 savings), and operating room cost ($41,078 savings). Adoption of the GYNECARE INTERCEED absorbable adhesion barrier for appropriate gynecologic surgeries would likely result in significant savings for hospitals, driven primarily by clinical patient benefits in terms of decreased length of stay and adhesion-related readmissions.

 

 

Tunis Med. 2015 Jul;93(7):407-12.

Medical treatment of endometriosis.

Derouich S, Attia L, Slimani O, Bouzid A, Mathlouthi N, Ben Temim R, Makhlouf T.

Abstract

PREREQUISITES:

Pathogenesis and pathophysiology of endometriosis, pharmacodynamics of oral contraceptives, progestagens, antiprogestagens, danazol, GnRh agonist and non-steroidal antiinflammatory.

PURPOSE OF REVIEW:

The aim of this paper is to systematically review the literature evidence of medical treatments for endometriosis and to summarize recently published recommendations.

METHODS:

Literature and recently published recommendations review via bibliographic research using Pubmed/Medline, Google scholar and Cochrane database.

RESULTS:

Endometriosis is an estrogen-dependent gynecological disease. Medical treatement of endometriosisinduce an estrogen deprivation situation. The Oral contraceptives reduce the rate of postoperative endometrioma recurrence and should be considered an essential part of long-term therapeutic strategies.New agents promise a distinct perspective in endometriosis treatment.

CONCLUSIONS:

The effectiveness of medical treatmentis well established in the management pelvic pain and infertility associated with endometriosis and constitutes an important alternative or complement to surgery.

 

 

Hum Reprod. 2016 Mar;31(3):554-62.

Endometriosis and fertility: women’s accounts of healthcare.

Young K¹, Fisher J², Kirkman M².

Abstract

STUDY QUESTION:

What do women with endometriosis recall being told about their fertility by their healthcare providers?

SUMMARY ANSWER:

Women recalled being given varied information and advice, and gave examples of empathic and individualized care from doctors but also reported opportunities for enhancing clinical practice.

WHAT IS KNOWN ALREADY:

There is evidence of an association between endometriosis and infertility. However, the strength of this association and the mechanisms that underlie it are not yet known nor are the implications for optimum healthcare.

STUDY DESIGN, SIZE, DURATION:

This study used in-depth cross-sectional qualitative research methods.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Women aged at least 18 years who lived in Victoria, Australia, and who had been surgically diagnosed with endometriosis were invited to participate in in-depth interviews about their experience of endometriosis. Twenty-six women of diverse backgrounds and experiences of endometriosis were interviewed from January to September 2014. Interviews were transcribed and analysed thematically using a data-driven approach.

MAIN RESULTS AND THE ROLE OF CHANCE:

All women encountered medical professionals who were aware of the association between endometriosis and infertility, and who were proactive in ensuring fertility was addressed within endometriosis care. Women recalled being given varied, often conflicting, information about the consequences for their fertility of an endometriosis diagnosis. While some recounted positive experiences with the way their doctor communicated with them about endometriosis and fertility, all women reported adverse experiences such as receiving insufficient or inappropriate information or having their doctor prioritize their fertility over other aspects of their care, including quality of life and symptom relief, without first consulting them.

LIMITATIONS, REASONS FOR CAUTION:

The perspectives of the women’s doctors were not sought. The findings may not translate to settings that differ from a predominantly Anglo-Saxon country with both universal public and private healthcare systems.

WIDER IMPLICATIONS OF THE FINDINGS:

Women’s fertility needs and priorities differ for many reasons; there can be no ‘one size fits all’ approach to care. Women may benefit most from endometriosis care in which they are first asked about their fertility needs and preferences and in which medical uncertainty is acknowledged.

STUDY FUNDING/COMPETING INTERESTS:

K.Y. receives a scholarship from the National Health and Medical Research Council and Australian Rotary Health. J.F. is supported by a Monash Professional Fellowship and the Jean Hailes Professional Fellowship which is funded by Perpetual Trustees Pty Ltd. The authors have no conflicts of interest to declare.

 

 

Clin Epigenetics. 2016 Jan 12;8:2.

The influence of menstrual cycle and endometriosis on endometrial methylome.

Saare M^#1,2,3, Modhukur V^#4, Suhorutshenko M¹, Rajashekar B⁴, Rekker K^1,2, Sõritsa D^1,2,5,6, Karro H^2,6, Soplepmann P⁶, Sõritsa A⁵, Lindgren CM⁷, Rahmioglu N⁷, Drong A⁷, Becker CM⁸, Zondervan KT^7,8, Salumets A^1,2,3, Peters M^1,2.

Abstract

BACKGROUND:

Alterations in endometrial DNA methylation profile have been proposed as one potential mechanism initiating the development of endometriosis. However, the normal endometrial methylome is influenced by the cyclic hormonal changes, and the menstrual cycle phase-dependent epigenetic signature should be considered when studying endometrial disorders. So far, no studies have been performed to evaluate the menstrual cycle influences and endometriosis-specific endometrial methylation pattern at the same time.

RESULTS:

Infinium HumanMethylation 450K BeadChip arrays were used to explore DNA methylation profiles of endometrial tissues from various menstrual cycle phases from 31 patients with endometriosis and 24 healthy women. The DNA methylation profile of patients and controls was highly similar and only 28 differentially methylated regions (DMRs) between patients and controls were found. However, the overall magnitude of the methylation differences between patients and controls was rather small (Δβ ranging from -0.01 to -0.16 and from 0.01 to 0.08, respectively, for hypo- and hypermethylated CpGs). Unsupervised hierarchical clustering of the methylation data divided endometrial samples based on the menstrual cycle phase rather than diseased/non-diseased status. Further analysis revealed a number of menstrual cycle phase-specific epigenetic changes with largest changes occurring during the late-secretory and menstrual phases when substantial rearrangements of endometrial tissue take place. Comparison of cycle phase- and endometriosis-specific methylation profile changes revealed that 13 out of 28 endometriosis-specific DMRs were present in both datasets.

CONCLUSIONS:

The results of our study accentuate the importance of considering normal cyclic epigenetic changes in studies investigating endometrium-related disease-specific methylation patterns.

 

 

Data Brief. 2015 Nov 17;5:971-4.

Supporting evidences for potential biomarkers of endometriosis detected in peripheral blood.

Signorile PG¹, Baldi A¹.

 

Abstract

Incidence of endometriosis is very high in women in the reproductive age (around 10%). To date, a reliable non-invasive diagnostic test for early diagnosis of endometriosis is not available. In this article we describe the potential value as diagnostic markers for endometriosis of two proteins (serum albumin and complement C3 precursor), previously identified as differentially expressed in women with endometriosis respect to healthy control by 2D gel analysis. A detailed description of the results obtained with this proteomic approach can be found in Signorile and Baldi [1]. ELISAs were performed on a large cohort of endometriosis (n=100) and healthy patients (n=10) to establish the differential expression of the identified proteins. ROC analyses confirmed the statistical significance of the differential expression of these proteins: serum albumin (p=0.028) ad complement C3 precursor (p=0.082). Evaluation of these two proteins, together with the already described Zn-alpha2-glycoprotein [1], could help in the early identification of endometriosis patients.

 

 

Am Fam Physician. 2016 Jan 1;93(1):41-8.

Common Questions About the Evaluation of Acute Pelvic Pain.

Bhavsar AK¹, Gelner EJ¹, Shorma T¹.

 

Abstract

Acute pelvic pain is defined as lower abdominal or pelvic pain of less than three months’ duration. It is a common presentation in primary care. Evaluation can be challenging because of a broad differential diagnosis and because many associated signs and symptoms are nonspecific. The most common diagnoses in reproductive-aged women with acute pelvic pain are idiopathic pelvic pain, pelvic inflammatory disease, acute appendicitis, ovarian cysts, ectopic pregnancy, and endometriosis. Among postmenopausal women, cancer must be considered. Findings from the history and physical examination can point to likely diagnoses, and laboratory testing and imaging can help confirm. Women of reproductive age should take a pregnancy test. In early pregnancy, transvaginal ultrasonography and beta human chorionic gonadotropin levels can help identify ectopic pregnancy and spontaneous abortion. For nonpregnant women, ultrasonography or computed tomography is indicated, depending on the possible diagnosis (e.g., ultrasonography is preferred when ovarian pathology is suspected). If ultrasonography results are nondiagnostic, magnetic resonance imaging can be helpful in pregnant women when acute appendicitis is suspected. If magnetic resonance imaging is unavailable, computed tomography may be indicated.

 

 

Hum Reprod. 2016 Mar;31(3):541-53.

Soft matrices inhibit cell proliferation and inactivate the fibrotic phenotype of deep endometriotic stromal cells in vitro.

Matsuzaki S¹, Canis M², Pouly JL³, Darcha C⁴.

Abstract

STUDY QUESTION:

Can deep infiltrating endometriotic stromal cells (DES) sense changes in extracellular matrix (ECM) stiffness and respond to them?

SUMMARY ANSWER:

Soft matrices inhibit cell proliferation and inactivate the fibrotic phenotype of DES in vitro.

WHAT IS KNOWN ALREADY:

Deep infiltrating endometriosis (DIE) is characterized histologically by dense fibrous tissue. Tissue stiffening is a hallmark of fibrosis. Studies show that matrix stiffness is involved in the progression of numerous diseases, including cancer and fibrosis. However, no studies to date have investigated whether tissue stiffening could influence cell behavior in DIE. Previous in vitro studies typically analyzed cells grown on rigid plastic or glass substrates with stiffness in the gigapascal (gPa) range, which is much stiffer than that occurring in vivo. To investigate how changes in ECM stiffness affect the behavior of DES, it is critical to model in vivo tissue compliance conditions in vitro.

STUDY DESIGN, SIZE, DURATION:

For this laboratory study, paired endometrial and endometriotic samples from 40 patients who had histological evidence of DIE and endometrial samples from 23 patients without endometriosiswere analyzed (uterine fibroma: n = 10, tubal infertility: n = 13).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

All participants were 20-37 years old and had regular menstrual cycles of 26-32 days. The abundance of F-actin, alpha smooth muscle actin (αSMA), Ki67, and procollagen type I in DES and endometrial stromal cells (EES) on polyacrylamide gel substrates of varying stiffness (2, 4, 8, 16 and/or 30 kPa) was determined by immunofluorescence confocal microscopy. mRNA level of type I collagen, matrix metalloproteinase-1 (MMP-1), MMP-14 and cyclin D1 was measured by real-time PCR. The cellular proliferation index (CPI), assessed as the percentage of Ki67-positive cells among the total number of nuclei stained by 4′,6-diamidino-2-phenylindole (DAPI) was determined.

MAIN RESULTS AND THE ROLE OF CHANCE:

Increased matrix stiffness induced F-actin stress fiber formation in both EES and DES, whereas αSMA-containing stress fibers were induced only in DES. Furthermore, increased stiffness increased the CPI in both EES (16 or 30 kPa versus 2 kPa, P < 0.05) and DES (16 or 30 kPa versus 2, 4 or 8 kPa, P < 0.05). Increased stiffness increased the percentage of procollagen I-positive cells as well as mRNA levels of type I collagen in both EES and DES in a matrix stiffness-dependent manner (2, 8 and 30 kPa) (P < 0.05). Increased stiffness also increased MMP-14 mRNA levels in EES (30 versus 2 kPa, P < 0.05), but decreased MMP-1 mRNA levels in DES in a matrix stiffness-dependent manner (2, 8 and 30 kPa; P < 0.05). Treatment with transforming growth factor (TGF)-β1 further increased type I collagen mRNA levels in both EES and DES when compared with cells grown on a substrate of the same stiffness (2, 8 or 30 kPa, with versus without TGF-β1, P < 0.05). Treatment with TGF-β1 also increased MMP-1 (8 or 30 kPa, P < 0.05 versus no TGF-β1) and MMP-14 mRNA levels (2, 8 or 30 kPa, P < 0.05 versus no TGF-β1) in EES, but decreased MMP-1 mRNA levels (2, 8 or 30 kPa, P < 0.05 versus no TGF-β1) in DES. On a soft substrate (2 kPa), both EES and DES exhibited a small rounded morphology with diffuse labeling for F-actin. No F-actin-positive stress fibers were observed in either EES or DES grown on 2 kPa substrates. There were more Ki67-positive EES when grown on 2, 4 or 8 kPa compared with Ki67-positive DES (P < 0.05).

LIMITATIONS, REASONS FOR CAUTION:

A tremendous gap exists between the present in vitro model and in vivo deep endometriotic tissues. Cell culture systems that more closely mimic the cellular complexity typical of in vivo endometriotic tissues are required to develop novel strategies for treatment of DIE. A disadvantage of polyacrylamide is its cytotoxicity but in the two-dimensional culture models used here, where cells are seeded above the polyacrylamide gel, this should not have a major impact. Finally, the soft substrates we used in vitro (2 and 4 kPa) may represent the elasticity of the endometrium in vivo, however, currently there are no data regarding tissue stiffness in DIE in vivo.

WIDER IMPLICATIONS OF THE FINDINGS:

Hormonal suppressive therapy is not usually effective for treating DIE. Interrupting the mechanical interactions between endometriotic fibroblasts and aberrant ECM may be a novel strategy for treatment of DIE.

STUDY FUNDING/COMPETING INTERESTS:

This study was supported in part by Karl Storz Endoscopy & GmbH (Tuttlingen, Germany). No competing interests are declared.

 

 

Pathol Int. 2016 Feb;66(2):108-13.

Adenocarcinoma arising in urinary bladder endocervicosis.

Nakaguro M^1,2, Tsuzuki T³, Shimada S^1,2, Taki T¹, Tsuchiyama M¹, Kitamura A¹, Suzuki Y¹, Nakano Y⁴, Ono K¹.

 

Abstract

Endocervicosis is a rare benign condition characterized by the presence of endocervical-type mucinous glands. Urinary bladder endocervicosis forms an elevated lesion in the posterior wall of the urinary bladder and is sometimes misdiagnosed as a malignant tumor clinically and pathologically. Herein we describe the first case of adenocarcinoma arising in urinary bladder endocervicosis. The patient, a 58-year-old woman, presented with asymptomatic hematuria. Cystoscopy revealed a nodular mass measuring 4 cm in diameter in the posterior wall, and total cystectomy was performed. Histology revealed that the elevated lesion of the bladder wall was composed of haphazard proliferation of cystic glands lined by benign endocervical-type epithelium. An adenocarcinoma arose at the center of this endocervicosis. Mucin histochemistry revealed the presence of sulfomucin in both the endocervicosis and adenocarcinoma components. Immunohistochemically, the endocervicosis was positive for cytokeratin (CK) 7, AE1/AE3, CAM5.2, HBME1, CA19-9, and estrogen receptor (ER), and negative for CK20, CDX2, progesterone receptor (PR), MUC5AC, and β-catenin. The adenocarcinoma showed similar immunohistochemical results, except for loss of ER expression and a slight increase in the ratio of Ki-67-positive cells. This case indicates that endocervicosis, known as a benign lesion, harbors the possibility of malignant transformation.

 

 

Reprod Sci. 2016 Aug;23(8):1011-8.

Role of Hormone Therapy After Primary Surgery for Endometrioma: A Multicenter Retrospective Cohort Study.

Seong SJ¹, Kim D², Lee KH³, Kim TJ⁴, Chung HH⁵, Chang SJ⁶, Lee EJ⁷.

 

Abstract

Endometriosis is a major cause of disability in women, and 40% to 50% of patients experience disease recurrence by 5 years after surgery. This multicenter retrospective cohort study (N = 588) determined the rate and risk factors for recurrent endometrioma after primary surgery and examined the role of postoperative hormone therapy. When recurrence was defined by sonographic identification of the endometrioma (≥20 mm in size), 61 (10.4%) patients experienced disease recurrence. The cumulative recurrence rates at 1, 2, 3, and 5 years after surgery were 2.2%, 4.9%, 6.9%, and 9.8%, respectively. To determine the risk factors for recurrence, the clinical factors of patients with and without recurrence were compared. There was a significantly increased risk of recurrence with posterior cul-de-sac (PCDS) obliteration (P = .031) and higher serum cancer antigen 125 (CA125) level (P = .005). A longer postoperative hormonal therapy duration (P < .01), absence of PCDS obliteration (P = .036), and lower serum CA125 level (P = .014) were associated with longer recurrence-free interval on multivariate analysis using the Cox regression model. Postoperative hormone therapy prolonged the interval from the time of surgery to the first recurrence. However, it did not prolong the interval from the end of treatment to the first recurrence. Our results indicate that although long-term postoperative hormone therapy might maintain minimal disease status, it does not control residual disease. Therefore, persistent hormone suppression should be used to prevent disease recurrence.

 

 

 

Ultrasound Obstet Gynecol. 2017 May;49(5):667

Performance of ultrasound-based endometriosis staging system (UBESS) for predicting level of complexity of laparoscopic surgery for endometriosis.

Menakaya U^1,2, Reid S³, Lu C⁴, Bassem G¹, Infante F¹, Condous G^1,5.

Abstract

OBJECTIVE:

To develop and assess the performance of a preoperative ultrasound-based endometriosis staging system (UBESS) to predict the level of complexity of laparoscopic surgery for endometriosis.

METHODS:

This was a multicenter prospective and retrospective cohort study on consecutive women with suspected endometriosis who underwent laparoscopy between June 2009 and July 2013. Each woman underwent a systematic transvaginal ultrasound evaluation to assess the pelvis for different phenotypes of endometriosis, and the diagnostic performance of ultrasound for these different phenotypes was evaluated relative to the gold standard, laparoscopy. A three-stage preoperative UBESS was developed to assess the severity of pelvic endometriosis, based on the histological phenotypes of endometriosis, the anatomical locations of deep infiltrating endometriosis and their sonographic markers of local invasiveness. The three stages of UBESS (I-III) were then correlated with the three levels of complexity of laparoscopic surgery for endometriosis described by the Royal College of Obstetricians and Gynaecologists (Levels 1-3). The end-points were the diagnostic performance of UBESS to predict the level of complexity of laparoscopic surgery for endometriosis, i.e. UBESS stage I to predict Level-1 laparoscopic surgery, UBESS stage II to predict Level-2 laparoscopic surgery and UBESS stage III to predict Level-3 laparoscopic surgery.

RESULTS:

The analysis included 192 women, with a mean ± SD age at diagnosis of endometriosis of 23.7 ± 9.3 years and a mean duration of symptoms prior to presentation of 42 months. Predominant reported locations of pelvic pain were left iliac fossa (32%), right iliac fossa (29.5%) and lower abdomen (61%) and predominant symptoms included dyspareunia (57.5%), dysmenorrhea (58.5%) and dyschezia (41.5%). The accuracy, sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of UBESS I for predicting a requirement for Level-1 laparoscopic surgery were: 87.5%, 83.3%, 91.7%, 90.9%, 84.6%, 10 and 0.182; those of UBESS II for predicting Level-2 surgery were: 87.0%, 73.7%, 90.3%, 65.1%, 93.3%, 7.6 and 0.292; and those of UBESS III for predicting Level-3 surgery were: 95.3%, 94.8%, 95.5%, 90.2%, 97.7%, 21.2 and 0.054, respectively.

CONCLUSION:

UBESS could be utilized to predict the level of complexity of laparoscopic surgery for endometriosis. It has the potential to facilitate the triage of women with suspected endometriosis to the most appropriate surgical expertise required for laparoscopic endometriosis surgery. UBESS needs to be validated externally in multiple centers to assess its general applicability. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

 

 

J Assist Reprod Genet

. 2016 Mar;33(3):317-323.

The role of fertility preservation in patients with endometriosis.

Carrillo L¹, Seidman DS², Cittadini E¹, Meirow D^3,4.

 

Abstract

Patients affected with severe endometriosis are at significant risk for ovarian tissue damage, which may lead to infertility, reduced response to ovarian stimulation, and occasionally, premature ovarian failure. The risk for a compromised ovarian reserve in young patients is especially high following repeated surgical intervention and in the presence of bilateral endometriomas. In many cases, enhanced loss of ovarian reserve may also result from the damaging effect of the pathologic process on follicle reservoir even without surgical interventions. Women diagnosed with severe endometriosis and those designated for extensive ovarian surgical intervention are frequently not planning to conceive. In light of recent advances in fertility preservation techniques (FPT), such as oocytes and ovarian tissue freezing, as well as their increasing success rates, we critically evaluate the options for FPT in patients suffering from endometriosis. Personalized counseling should be offered to all patients with endometriosis taking into account age, extent of ovarian involvement, current ovarian reserve, previous and impending surgeries for endometriosis, along with current success rates and possible risks associated with FPT.

 

 

Int J Clin Exp Med. 2015 Oct 15;8(10):17757-64.

MiR-202 promotes endometriosis by regulating SOX6 expression.

Zhang D¹, Li Y¹, Tian J¹, Zhang H¹, Wang S¹.

Abstract

OBJECTIVES:

This study is to investigate the role and mechanism of microRNA-202 (miR-202) in endometriosis.

METHODS:

Forty-five cases of ectopic endometrial tissues, 25 cases of eutopic endometrial tissues and 26 cases of normal endometrial tissues were collected. MiR-202 expression was detected by quantitative RT-PCR. The protein expressions of SOX6 (sex determining region Y-box 6) and its downstream proteins (p21, cyclin D1 and pRb (retinoblastoma protein)) were detected by immunochemistry and western blot. MTT and transwell assays were used to examine cell proliferation and cell migration. The dual luciferase assay was applied to validate whether miR-202 can directly target SOX6 gene.

RESULTS:

MiR-202 was highly expressed in eutopic and ectopic endometrial tissues than normal endometrial tissues (P < 0.05), and the expression was higher in tissues with III/IV stages than I/II stages (P < 0.05). The expression of SOX6 protein was lower in ectopic endometrial tissues than in normal endometrial tissues. In ectopic endometrial tissues, the expression of p21 was decreased while cyclin D1 and pRb was up-regulated than in normal endometrial tissues (P < 0.05). In cultured endometrial cells, miR-202 down-regulation induced up-regulation of SOX6 and p21 whereas down-regulation of cyclin D1 and pRb. MiR-202 promoted the proliferation and metastasis of endometrial cells. And, miR-202 could complementary bind to SOX6 3’UTR to regulate the expression of SOX6.

CONCLUSION:

MiR-202 was up-regulated in the endometriosis. Through targeting SOX6 and its downstream proteins (p21, cyclin D1 and pRb), miR-202 can promote the progression of endometriosis.

 

 

Minerva Ginecol. 2016 Feb;68(1):49-54.

Role of robotic surgery in the management of deep infiltrating endometriosis.

Sussfeld J¹, Segaert A, Rubod C, Collinet P.

 

Abstract

Standard laparoscopy (SL) is the gold standard for endometriosis surgery including deep infiltrating endometriosis(DIE). DIE laparoscopic surgery can require complex surgical procedures performed by multidisciplinary surgical team. Robotic assisted laparoscopy (RAL) could offer technical advantages such as 3D vision, tremor filtration and better surgical ergonomy. RAL would be able to improve surgical performances compared to SL, decrease perioperative morbidity and decrease the risk of laparo-conversion. For these reasons, DIE could be one of the best indications for RAL in gynecologic surgery. Demonstrating the feasibility of RAL for DIE surgery, few series of cases have been already published. None of them have demonstrated differences in surgical outcomes. One randomized control trial comparing SL to RAL would be mandatory in order to define potential benefits of RAL for DIE surgery.

 

 

 

Int J Mol Sci. 2016 Jan 13;17(1).

iRNAs Regulation and Its Role as Biomarkers in Endometriosis.

Marí-Alexandre J¹, Sánchez-Izquierdo D², Gilabert-Estellés J³, Barceló-Molina M⁴, Braza-Boïls A⁵, Sandoval J⁶.

 

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs (18-22 nt) that function as modulators of gene expression. Since their discovery in 1993 in C. elegans, our knowledge about their biogenesis, function, and mechanism of action has increased enormously, especially in recent years, with the development of deep-sequencing technologies. New biogenesis pathways and sources of miRNAs are changing our concept about these molecules. The study of the miRNA contribution to pathological states is a field of great interest in research. Different groups have reported the implication of miRNAs in pathologies such as cancer, diabetes, cardiovascular, and gynecological diseases. It is also well-known that miRNAs are present in biofluids (plasma, serum, urine, semen, and menstrual blood) and have been proposed as ideal candidates as disease biomarkers. The goal of this review is to highlight the current knowledge in the field of miRNAs with a special emphasis to their role in endometriosis and the newest investigations addressing the use of miRNAs as biomarkers for this gynecological disease.

 

 

J Minim Invasive Gynecol. 2016 May-Jun;23(4):476-88.

Adenomyosis: What the Patient Needs.

Alabiso G¹, Alio L², Arena S³, Barbasetti di Prun A¹, Bergamini V⁴, Berlanda N⁵, Busacca M¹, Candiani M⁶, Centini G⁷, Di Cello A⁸, Exacoustos C⁹, Fedele L⁵, Fuggetta E¹⁰, Gabbi L¹¹, Geraci E¹², Imperiale L¹⁰, Lavarini E⁴, Incandela D², Lazzeri L⁷, Luisi S⁷, Maiorana A², Maneschi F¹³, Mannini L¹⁴, Mattei A¹⁴, Muzii L¹⁰, Pagliardini L⁶, Perandini A⁴, Perelli F¹⁴, Pinzauti S⁷, Porpora MG¹⁵, Remorgida V¹¹, Leone Roberti Maggiore U⁶, Seracchioli R¹², Solima E¹, Somigliana E¹⁶, Tosti C⁷, Venturella R⁸, Vercellini P⁵, Viganò P⁶, Vignali M¹, Zannoni L¹², Zullo F⁸, Zupi E⁹; Endometriosis Treatment Italian Club.

 

Abstract

A panel of experts in the field of endometriosis expressed their opinions on management options in a 28-year-old patient, attempting pregnancy for 1 year, with severe cyclic pelvic pain and with clinical examination and imaging techniques suggestive of adenomyosis. Many questions this paradigmatic patient may pose to the clinician are addressed, and all clinical scenarios are discussed. A decision algorithm derived from this discussion is also proposed.

 

 

 

Fertil Steril. 2016 Apr;105(4):997-1002.

Potential influence of in utero and early neonatal exposures on the later development of endometriosis.

Vannuccini S¹, Lazzeri L¹, Orlandini C¹, Tosti C¹, Clifton VL², Petraglia F³.

Abstract

OBJECTIVE:

To investigate the possible correlation between maternal characteristics, in utero and early neonatal life exposures, and the development of endometriosis in adult life.

DESIGN:

Case-control study.

SETTING:

University hospital.

PATIENT(S):

A group of 161 patients with endometriosis and a control group of 230 women undergoing laparoscopy for benign adnexal diseases and free of endometriosis.

INTERVENTION(S):

All women included in the study were requested to answer a series of questions about their mothers’ gestational data and on their own perinatal and early postnatal lives.

MAIN OUTCOME MEASURE(S):

Odds ratio, adjusted odds ratios, and 95% confidence intervals for the associations between maternal characteristics during the patient’s pregnancy, in utero exposure to obstetrical and perinatal complications, and the type of feeding received during the neonatal period with the development of endometriosis in adult life.

RESULT(S):

Mothers of women with endometriosis were significantly more likely to be affected by endometriosisor uterine fibroids, with a higher incidence of smoking during pregnancy. Women with endometriosis were more frequently born prematurely, with a significantly lower birth weight, and their mothers experienced preeclampsia during their pregnancies more often than control subjects. They were also more frequently formula fed than breast fed in early life. However, only prematurity and formula feeding were retained in the multivariate analysis model.

CONCLUSION(S):

Among intrauterine and early neonatal exposures, prematurity and formula feeding were risk factors for the development of endometriosis in adult life. Further studies should evaluate the underlying biologic mechanisms.

 

 

Fertil Steril. 2016 Apr;105(4):988-96.

Vascular endothelial growth factor pathway in endometriosis: genetic variants and plasma biomarkers.

Vodolazkaia A¹, Yesilyurt BT², Kyama CM³, Bokor A⁴, Schols D⁵, Huskens D⁵, Meuleman C⁶, Peeraer K⁶, Tomassetti C⁶, Bossuyt X¹, Lambrechts D², D’Hooghe T⁷, Fassbender A⁸.

Abstract

OBJECTIVE:

To study single nucleotide polymorphisms (SNPs) involved in angiogenesis (VEGF, PLGF, VEGFR1, VEGFR2, HIF-1α) and plasma levels of the corresponding proteins (VEGF, PLGF, sVEGFR1, sVEGFR2) in women with and without endometriosis.

DESIGN:

Allele frequencies of vascular endothelial growth factor (VEGF) pathway SNPs and plasma levels of the corresponding proteins were investigated in patients with endometriosis and in controls.

SETTING:

University hospital.

PATIENT(S):

Samples of DNA from 1,931 Caucasian patients were included (1,109 patients with endometriosisand 822 controls). An additional study group included 973 DNA samples from volunteers, self-reported to be healthy without laparoscopic evaluation.

INTERVENTION(S):

Women who underwent a laparoscopy for subfertility and/or pain and healthy volunteers without laparoscopic evaluation.

MAIN OUTCOME MEASURE(S):

Functional SNPs of the VEGF, VEGFR1, VEGFR2, HIF-1α genes and Hap Map tagging SNPs of the PLGF gene were genotyped by using iPLEX technology on a Sequenom MassArray and TaqMan SNP Genotyping Assay. The VEGF levels were determined in ethylenediaminetetraacetic acid plasma samples by using Bio-Plex Protein Array System. PLGF, sVEGFR1, and sVEGFR2 levels were measured in ethylenediaminetetraacetic acid plasma samples by using ELISA Quantikine kits.

RESULT(S):

A significant association was found between the rs2268613 polymorphism in the PLGF gene and PLGF plasma levels. In all study subjects, women with the AA variant of the rs2268613 PLGF gene had significantly lower PLGF plasma levels (median [interquartile range] 9.36 [8.19-10.43] pg/mL) than those with the AG variant (12.1 [11.81-20.84] pg/mL; P(a)=.0085, P(b)=.04), both before and after multiple testing. Plasma levels of VEGF were elevated in endometriosis patients (especially in minimal-mild endometriosis during the menstrual cycle phase) compared with laparoscopic controls but had a moderate diagnostic performance (area under the curve, 0.73) in this discovery dataset. At a cut-off plasma level of VEGF >3.88 pg/mL, minimal-mild stages of endometriosis were diagnosed with a sensitivity of 74% and a specificity of 80% during the menstrual phase of cycle. The associations between the presence of endometriosis and SNPs in PLGF (rs2268614), HIF-1α (rs11549465), and VEGFR1 (rs9582036) genes lost statistical significance after multiple testing.

CONCLUSION(S):

Genetic variants in the PLGF rs2268613 gene may influence plasma levels of the corresponding protein. Plasma levels of VEGF were elevated in endometriosis patients compared with controls. The associations between the presence of endometriosis and SNPs in PLGF (rs2268614), HIF-1α (rs11549465), and VEGFR1 (rs9582036) genes lost statistical significance after multiple testing.

 

 

Eur J Obstet Gynecol Reprod Biol. 2016 Feb;197:159-63.

Effect of imatinib on growth of experimental endometriosis in rats.

Yildiz C¹, Kacan T², Akkar OB³, Karakus S³, Seker M², Kacan SB⁴, Ozer H⁵, Cetin A³.

Abstract

OBJECTIVE:

Currently, medical and surgical treatment options for endometriosis are limited due to suboptimal efficacy, and also safety and tolerance issues. Long-term use of gonadotrophin-releasing hormone analogs, androgenes, and the danazol, which are widely used drugs for endometriosis, is usually not possible due to their suboptimal safety and tolerance profile. The lack of an effective, tolerable and safe treatment option for endometriosis makes animal models of experimental endometriosis necessary to study candidate drugs. The aim of this study was to investigate the efficacy of imatinib on the experimental endometriosis in a rat model.

STUDY DESIGN:

Endometriosis was induced by autotransplantation of uterine tissue into the peritoneal cavity. Twenty-four rats, which had visually confirmed endometriotic implants on subsequent laparotomy, were randomized into three groups to receive imatinib (25mg/kg/day, p.o.), anastrozole (0.004 mg/day, p.o.), or normal saline (0.1 mL, i.p.) for 14 days. After removal of endometriotic tissue and H & E staining, endometriosis score was determined according to a semiquantitative histological classification. Also, immunostaining with primary antibodies including VEGF, CD117, and Bax were used for immunohistochemical (IHC) examination.

RESULTS:

Both anastrozole and imatinib suppressed the growth of endometriotic tissue and reduced the number of ovarian follicles. Although the difference was not statistically significant, imatinib was less effective than anastrozole for treatment of endometriosis.

CONCLUSION:

Imatinib effectively treats experimental endometriosis by its inhibitor effects on angiogenesis and cell proliferation.

 

 

J Reprod Med. 2015 Nov-Dec;60(11-12):480-90.

Birth Outcomes by Infertility Diagnosis Analyses of the Massachusetts Outcomes Study of Assisted Reproductive Technologies (MOSART).

Luke B, Stern JE, Kotelchuck M, Declercq ER, Cohen B, Diop H.

Abstract

OBJECTIVE:

To evaluate assisted reproductive technology (ART) pregnancy outcomes by infertility diagnosis.

STUDY DESIGN:

ART data on women who were treated and gave birth in Massachusetts were linked to vital records and hospital utilization data. Live births were categorized by 8 mutually exclusive ART diagnoses. Risks of prematurity, low birthweight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA), pregnancy hypertension, gestational diabetes, prenatal hospitalizations, and primary cesarean delivery were modeled using logistic regression, adjusted for parental characteristics, treatment parameters, and plurality (adjusted odds ratios [AORs] and 95% confidence intervals); the reference group were pregnancies with the diagnosis of malefactor.

RESULTS:

Among the 7,354 singleton and twin pregnancies, there were nonsignificant differences in the risks for LBW, SGA, or LGA. Significantly increased risks included gestational diabetes (ovulation disorders, AOR 1.80, 1.35-2.41), prematurity (ovulation disorders, AOR 1.36, 1.08-1.71; other factors, AOR 1.33, 1.05-1.67), prenatal hospital admissions (endometriosis, tubal and other factors, ovulation disorders, and uterine factors, AORs ranging from 1.66-2.68), and primary cesarean section (uterine factors, AOR 1.96, 1.15-3.36).

CONCLUSION:

Although the infant outcomes of LBW, SGA, and LGA were generally similar across diagnosis groups, specific diagnoses had greater risks for prematurity, gestational diabetes, prenatal hospital utilization, and primary cesarean delivery. (J Reprod Med 2015;

 

 

Expert Rev Gastroenterol Hepatol. 2016 Jul;10(7):785-94.

CT Colonography: an update on current and future indications.

Laghi A¹.

 

Abstract

Computed tomographic colonography (CTC) is a minimally invasive, patient-friendly, safe and robust colonic imaging modality. The technique is standardized and consolidated evidence from the literature shows that the diagnostic performances for the detection of colorectal cancer and large polyps are similar to colonoscopy (CS) and largely superior to alternative radiological exams, like barium enema. A clear understanding of the exact role of CTC will be beneficial to maximize the benefits and minimize the potential sources of frustration or disappointment for both referring clinicians and patients. Incomplete, failed, or unfeasible CS; investigation of elderly, and frail patients and assessment of diverticular disease are major indications supported by evidence-based data and agreed by the endoscopists. The use of CTC for symptomatic patients, colorectal cancer screening and colonic surveillance is still under debate and, thus, recommended only if CS is unfeasible or refused by patients.

 

 

Cell Death Dis. 2016 Jan 14;7

Effect of hydroxychloroquine and characterization of autophagy in a mouse model of endometriosis.

Ruiz A¹, Rockfield S¹, Taran N¹, Haller E², Engelman RW³, Flores I^4,5, Panina-Bordignon P⁶, Nanjundan M¹.

 

Abstract

In endometriosis, the increased survival potential of shed endometrial cells (which normally undergo anoikis) is suggested to promote lesion development. One mechanism that may alter anoikis is autophagy. Using an autophagic flux inhibitor hydroxychloroquine (HCQ), we identified that it reduces the in vitro survival capacity of human endometriotic and endometrial T-HESC cells. We also identified that HCQ could decrease lesion numbers and disrupt lesion histopathology, as well as increase the levels of peritoneal macrophages and the IP-10 (10 kDa interferon-γ-induced protein) chemokine in a mouse model of endometriosis. We noted that RNA levels of a subset of autophagic markers were reduced in lesions relative to uterine horns from endometriosis-induced (untreated) mice. In addition, the RNA levels of autophagic markers were decreased in uterine horns of endometriosis-induced mice compared with those from controls. However, we noted that protein expression of LC3B (microtubule-associated protein 1 light-chain 3β; an autophagic marker) was increased in uterine horns of endometriosis-induced mice compared with uterine horns of controls. By immunohistochemical staining of a human endometriosis-focused tissue microarray, we observed LC3B expression predominantly in epithelial relative to stromal cells in both eutopic and ectopic endometria. Via transmission electron microscopy, cells from eutopic endometria of endometriosis-induced mice contained more lipid droplets (rather than autophagosomes) compared with uterine horns from controls. Collectively, our findings indicate that the autophagic pathway is dysregulated in both ectopic and eutopic endometrium in a murine model of endometriosis and that HCQ has potential as a therapeutic agent for women afflicted with endometriosis.

 

 

Mol Cell Endocrinol. 2016 Mar 15;424:42-9.

Potential role of estrogen in maintaining the imbalanced sympathetic and sensory innervation in endometriosis.

Liang Y¹, Yao S².

 

Abstract

Endometriosis, one of the most common benign gynecological diseases, affects millions of women of childbearing age. Endometriosis-associated pain is a major cause of disability and compromised quality of life in women. Neuropathic mechanisms are believed to play an important role. An imbalanced sympathetic and sensory innervation (reduced sympathetic innervation, with unchanged or increased sensory innervation in endometriotic lesions) has been demonstrated in endometriosis in recent studies. And it is believed to contribute to the pathogenesis of endometriosis-associated pain. It is primarily considered to be a natural adaptive program to endometriosis-associated inflammation. However, it is important to further clarify whether other potential modulating factors are involved in this dysregulation. It is generally accepted that endometriosis is an estrogen dependent disease. Higher estrogen biosynthesis and lower estrogen inactivation in endometriosis can lead to an excess of local estrogen in endometriotic lesions. In addition to its proliferative and anti-inflammatory actions, local estrogen in endometriosis also exerts potential neuromodulatory effects on the innervation in endometriosis. The aim of this review is to highlight the role of estrogen in mediating this imbalanced sympathetic and sensory innervation in endometriosis, through direct and indirect mechanisms on sympathetic and sensory nerves. Theoretical elaboration of the underlying mechanisms provides new insights in supporting the therapeutic role of estrogen in endometriosis-associated pain.

 

 

Am J Obstet Gynecol. 2016 Apr;214(4):452-464.

Variation in outcome reporting in endometriosis trials: a systematic review.

Hirsch M¹, Duffy JM², Kusznir JO³, Davis CJ³, Plana MN⁴, Khan KS³; International Collaboration to Harmonize Outcomes and Measures for Endometriosis.

Abstract

OBJECTIVE:

We reviewed the outcomes and outcome measures reported in randomized controlled trials and their relationship with methodological quality, year of publication, commercial funding, and journal impact factor.

DATA SOURCES:

We searched the following sources: (1) Cochrane Central Register of Controlled Trials, (2) Embase, and (3) MEDLINE from inception to November 2014.

STUDY ELIGIBILITY:

We included all randomized controlled trials evaluating a surgical intervention with or without a medical adjuvant therapy for the treatment of endometriosis symptoms.

STUDY DESIGN:

Two authors independently selected trials, assessed methodological quality (Jadad score; range, 1-5), outcome reporting quality (Management of Otitis Media with Effusion in Cleft Palate criteria; range, 1-6), year of publication, impact factor in the year of publication, and commercial funding (yes or no). Univariate and bivariate analyses were performed using Spearman Rh and Mann-Whitney U tests. We used a multivariate linear regression model to assess relationship associations between outcome reporting quality and other variables.

RESULTS:

There were 54 randomized controlled trials (5427 participants), which reported 164 outcomes and 113 outcome measures. The 3 most commonly reported primary outcomes were dysmenorrhea (10 outcome measures; 23 trials), dyspareunia (11 outcome measures; 21 trials), and pregnancy (3 outcome measures; 26 trials). The median quality of outcome reporting was 3 (interquartile range 4-2) and methodological quality 3 (interquartile range 5-2). Multivariate linear regression demonstrated a relationship between outcome reporting quality with methodological quality (β = 0.325; P = .038) and year of publication (β = 0.067; P = .040). No relationship was demonstrated between outcome reporting quality with journal impact factor (Rho = 0.190; P = .212) or commercial funding (P = .370).

CONCLUSION:

Variation in outcome reporting within published endometriosis trials prohibits comparison, combination, and synthesis of data. This limits the usefulness of research to inform clinical practice, enhance patient care, and improve patient outcomes. In the absence of a core outcome set for endometriosis we recommend the use of the 3 most common pain (dysmenorrhea, dyspareunia, and pelvic pain) and subfertility (pregnancy, miscarriage, and live birth) outcomes. International consensus among stakeholders is needed to establish a core outcome set for endometriosis trials.

 

 

Front Endocrinol (Lausanne). 2016 Jan 6;6:192

Proteome-Wide Effect of 17-β-Estradiol and Lipoxin A4 in an Endometriotic Epithelial Cell Line.

Sobel JA¹, Waridel P², Gori I³, Quadroni M², Canny GO⁴.

 

Abstract

Endometriosis affects approximately 10% of women of reproductive age. This chronic, gynecological inflammatory disease results in a decreased quality of life for patients, with the main symptoms including chronic pelvic pain and infertility. The steroid hormone 17-β Estradiol (E2) plays a key role in the pathology. Our previous studies showed that the anti-inflammatory lipid Lipoxin A4 (LXA4) acts as an estrogen receptor-alpha agonist in endometrial epithelial cells, inhibiting certain E2-mediated effects. LXA4 also prevents the progression of endometriosis in a mouse model via anti-proliferative mechanisms and by impacting mediators downstream of ER signaling. The aim of the present study was therefore to examine global proteomic changes evoked by E2 and LXA4 in endometriotic epithelial cells. E2 impacted a greater number of proteins in endometriotic epithelial cells than LXA4. Interestingly, the combination of E2 and LXA4 resulted in a reduced number of regulated proteins, with LXA4 mediating a suppressive effect on E2-mediated signaling. These proteins are involved in diverse pathways of relevance to endometriosis pathology and metabolism, including mRNA translation, growth, proliferation, proteolysis, and immune responses. In summary, this study sheds light on novel pathways involved in endometriosis pathology and further understanding of signaling pathways activated by estrogenic molecules in endometriotic epithelial cells.

 

 

 

 

Semin Immunopathol. 2016 Nov;38(6):651-668.

Mouse is the new woman? Translational research in reproductive immunology.

Clark DA¹.

 

Abstract

In an outbred mating typical of human reproduction, the embryo and feto-placental unit express paternal antigens to which the mother’s immune system can react. However, the embryo and feto-placental unit can engineer the maternal immune defense system towards helpful rather than harmful reactions. Indeed, this begins with the prospective mother’s exposure to paternal seminal plasma. In this review, the pregnancy complications of implantation failure (infertility), recurrent spontaneous abortion, pre-eclampsia and intrauterine growth restriction, and premature labor are examined to determine the degree of similarity between events in women and events in lab mouse models. The artificially induced model of endometriosis (which contributes to infertility) is also compared to what occurs in women. One may conclude that the female mouse provides a good analog of the human female. Nevertheless, it is always important to validate mouse data with human studies. The discussion focuses on the intrauterine interface between embryonic and placental tissues and maternal uterine tissues and the dialogue that is referred to as cross-talk. Issues relating to bidirectional transplacental traffic of immune system cells are not discussed as there is very little relevant data.

 

 

Am J Reprod Immunol. 2016 Mar;75(3):411-7

Uterine Leukocyte Function and Dysfunction: A Hypothesis on the Impact of Endometriosis.

Parkin KL^1,2, Fazleabas AT¹.

 

Abstract

Endometriosis is a chronic inflammatory disease characterized by the growth of endometrial glands and stroma outside of the uterus. The disease affects approximately 10-15% of women of reproductive age and presents with clinical symptoms of pelvic pain and infertility. Changes in the leukocyte populations within the ectopic tissue and eutopic endometrium have been reported, and data suggest these alterations contribute to the pathology and symptoms of the disease. In this review, we discussed differences when comparing uterine NK cells and regulatory T cells within the eutopic endometrium between patients with endometriosis and healthy patients, and how these differences relate to implantation failure and/or decreased clearance of menstrual tissue in patients with the disease. The data demonstrate a critical need to examine endometrium and menstrual tissue in patients with endometriosis excluded from studies examining unknown causes of infertility and heavy menstrual bleeding. The information gathered from excluded patients will further enhance our understanding of how the immune system contributes to the pathophysiology of endometriosis and help to identify biomarkers for patients at higher risk for developing endometriosis-associated infertility.

 

 

Am J Reprod Immunol. 2016 Apr;75(4):486-92.

Resveratrol Enhances Apoptosis in Endometriotic Stromal Cells.

Taguchi A¹, Koga K¹, Kawana K¹, Makabe T¹, Sue F¹, Miyashita M¹, Yoshida M¹, Urata Y¹, Izumi G¹, Tkamura M¹, Harada M¹, Hirata T¹, Hirota Y¹, Wada-Hiraike O¹, Fujii T¹, Osuga Y¹.

Abstract

PROBLEM:

Resistance to apoptosis, together with inflammatory and invasive activity, contributes to the pathogenesis of endometriosis; therefore, approaches that can safely enhance apoptosis in endometriotic tissue are highly sought after as a means of managing the disease. Although resveratrol (RVT) is known to induce apoptosis or increase sensitivity to apoptotic stimuli in various cancer cell types, its effect on human endometriosishas remained uncertain. This study aimed to investigate whether RVT induces or enhances apoptosis in human endometriotic stromal cells (ESCs).

METHOD OF STUDY:

Endometriotic tissues were collected, during laparoscopies, from women affected by ovarian endometriosis. ESCs were prepared, cultured, and treated with RVT. Apoptosis was assessed by annexin V-PI staining. Survivin mRNA expression in ESCs was examined using RT-PCR. ESCs were pre-treated with or without RVT and then incubated with TNF-α-related-apoptosis-inducing ligand (TRAIL), which is a known pro-apoptotic molecule.

RESULTS:

RVT alone did not induce apoptosis in ESCs. RVT significantly reduced survivin mRNA expression (P < 0.05). Pre-treatment with RVT significantly enhanced TRAIL-induced apoptosis (8.13 ± 0.83% (control) versus 29.19 ± 7.39% (pre-treated with RVT), P < 0.05).

CONCLUSION:

This study indicates that RVT suppresses survivin expression and enhances TRAIL-induced apoptosis in ESCs.

 

 

 

 

 

J Obstet Gynaecol Res. 2016 Mar;42(3):350-2.

Huge ovarian endometrioma that grew after menopause: Case report.

Matsushima T¹, Asakura H¹.

 

Abstract

Endometriomas occur in women of reproductive age and are rare after menopause. A 56-year-old gravida 3 para 2 woman complained of abdominal fullness that had gradually worsened over approximately one year (i.e. 5 years postmenopause). Diagnostic imaging revealed a cystic lesion that extended to just below the diaphragm. An ovarian cystoma of low malignancy was suspected. The preoperative blood test indicated normal estradiol levels at 12.6 pg/mL. She underwent bilateral adnexectomy and total hysterectomy. The appendages on the affected (i.e. right) side weighed approximately 12 kg. An ovarian endometrioma with benign pathology was diagnosed. Postmenopausal endometrioma can occur even in patients with normal postmenopausal estradiol values who are not receiving exogenous hormones. These patients require careful follow-up.

 

 

Can Urol Assoc J. 2015 Nov-Dec;9(11-12):E921-4.

Evaluation of risk factors and treatment options in patients with ureteral stricture disease at a single institution.

Tran H¹, Arsovska O¹, Paterson RF¹, Chew BH¹.

Abstract

INTRODUCTION:

Ureteral strictures are a significant cause of morbidity and mortality, resulting in potential kidney damage requiring several surgical procedures. Non-malignant causes include radiation, trauma from calculi impaction, pelvic surgery, or ureteroscopy (URS). We identified risk factors in our patients with ureteral strictures and the success of their treatment outcomes.

METHODS:

A retrospective chart review of 25 patients with 29 ureteral strictures was performed to determine the success of their treatment.

RESULTS:

Twenty-five (25) patients with 29 benign ureteral strictures were identified. Most cases (60%) were caused by impacted stones where the median stone size was 1.15 cm (0.37-1.8 cm). Intervention for stones prior to stricture development included shockwave lithotripsy, URS, and percutaneous nephrolithotomy. Five patients with strictures from impacted stones had ureteric complications during stone treatment including perforation +/- urinoma (n=3), fractured guidewire left in situ (n=1), and ureteric orifice resection (n=1). Other stricture etiologies included radiation (28%) and endometriosis (4%). Treatment modalities used included ureteroureterostomy (n=2), ureteral re-implant (n=3), urinary diversion (n=3), autotrasplant (n=1), laser endoureterotomy +/- balloon dilation (n=8), nephrectomy (n=2), balloon dilation +/- stent (n=3), ureterovesical junction (UVJ) resection + stent (n=1), chronic stent changes (n=4), or surveillance (n=3).

CONCLUSIONS:

Our evaluation highlights important principles. Patients with complicated ureteroscopies or severely impacted calculi warrant close followup with imaging after stone treatment due to possibility of rapid renal deterioration from stricture formation. Radiation-induced strictures are difficult to manage, possibly requiring subsequent urinary diversion. Finally, endoscopic management of benign ureteral strictures via balloon dilation and laser endoureterotomy is an excellent choice in properly selected patients, with opportunity for subsequent salvage treatments if needed.

 

 

J Womens Health (Larchmt). 2016 Jun;25(6):646-53.

Age-Related Differences in Quality of Life in Swedish Women with Endometriosis.

Lövkvist L¹, Boström P¹, Edlund M¹, Olovsson M².

Abstract

OBJECTIVE:

The purpose of this observational study was to evaluate the impact of endometriosis on quality of life (QoL) in different age groups of Swedish women with endometriosis. Recruitment occurred through the Endometriosis Association (Sweden) (n = 400) and five gynecology departments of five Swedish hospitals (n = 400). All voluntary female members of the patient organization and patients attending specialist clinics due to endometriosis (n = 800) were invited by sending them a questionnaire. An age- and gender-matched sample of the general Swedish population was used as a control group when analyzing SF-36 data.

METHODS:

A postal questionnaire (including SF-36) was distributed to 800 women. The questionnaire was evaluated by using descriptive statistics, and SF-36 was evaluated according to standard methods.

RESULTS:

Of the 449 (56%) self-administered questionnaires returned, 431 (96%) contained evaluable answers. Women with endometriosis have significantly lower SF-36 scores than the general female Swedish population, and the score depends on the women’s age. Younger women experience more symptoms and have a lower QoL score compared with women in the older age group.

CONCLUSION:

Women with endometriosis have significantly lower QoL than the general female Swedish population and it depends on the women’s age, where younger women express more symptoms and have a lower QoL compared with women in the older age group. Our results highlight that more healthcare resources should be focused on younger women with endometriosis.

 

 

Am J Reprod Immunol. 2016 Apr;75(4):493-502.

Increased uNK Progenitor Cells in Women With Endometriosis and Infertility are Associated With Low Levels of Endometrial Stem Cell Factor.

Thiruchelvam U¹, Wingfield M^2,3, O’Farrelly C^1,4.

Abstract

PROBLEM:

Uterine natural killer (uNK) cells play a significant role in successful human pregnancy. Having previously demonstrated uNK cell progenitors in human endometrium, we hypothesized that abnormal uNK cell maturation contributes to infertility in women with endometriosis. We aimed to characterize uNK cells at different developmental stages in women with and without endometriosis and to investigate possible mechanisms to explain any differences.

METHOD OF STUDY:

We characterized uNK cell development in women with and without endometriosis using flow cytometry, protein array and in vitro experiments.

RESULTS:

We found increased proportions of uNK cells at developmental stages 1 and 2 in endometrium from women with endometriosis (n = 36; mean = 21.2%) when compared with healthy fertile women (n = 9; mean = 7.0%). Protein array analysis revealed significantly lower levels of stem cell factor (SCF) in the eutopic endometrium of women with endometriosis when compared to healthy women. Addition of SCF to endometrial progenitor cells in vitro restored uNK cell maturation.

CONCLUSION:

We have shown that women with endometriosis have low levels of endometrial SCF, which we hypothesize contributes to abnormal maturation of local uNK cell populations. This defect may also compromise embryo implantation and hence contribute to endometriosis-associated infertility. SCF replacement may be a new therapeutic approach.

 

 

Med J Islam Repub Iran. 2015 Oct 19;29:280.

A comparison between serum levels of interleukin-6 and CA125 in patients with endometriosis and normal women.

Kashanian M¹, Sariri E², Vahdat M³, Ahmari M⁴, Moradi Y⁵, Sheikhansari N⁶.

Abstract

BACKGROUND:

The purpose of the present study was to compare the serum levels of IL6 and CA125 in women with and without endometriosis. They were also compared in mild, moderate and severe cases.

METHODS:

In this case-control study, CA125 and IL6 levels in 76 women with laparoscopic proven endometriosiswere compared with 76 women without evidence of endometriosis. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were then calculated for each test.

RESULTS:

Both groups did not show significant difference in their age, BMI, ESR and gravidity. Mean serum levels of IL-6 and CA125 were significantly higher in the case group (30.4±6.43 vs 13.9±3.17 Pg/ml and 62.6±10.69 vs 16.6±1.79 IU/ml respectively). Considering a cutoff point of 30 Pg/ml for IL-6, sensitivity, specifically, PPV and NPV value of 21.1%, 66.6%, 86.8% and 23.37% were obtained, respectively. Considering a cutoff point of 35 IU/ml for CA125, sensitivity, specifically, PPV and NPV were 44.76%, 94.73%, 89.47% and 63.15%, respectively. Area under the ROC curve was 0.69 for CA125 and 0.54 for IL6, which showed a low value for these tests.

CONCLUSION:

Although CA125 and IL-6 were higher than normal controls in endometriosis, area under the ROC curve, did not show significant any diagnostic value for these tests.

 

 

J Menopausal Med. 2015 Dec;21(3):142-8.

Serum Anti-Müllerian Hormone Levels before Surgery in Patients with Ovarian Endometriomas Compared to Other Benign Ovarian Cysts.

Jeon JH¹, Park SY¹, Lee SR¹, Jeong K¹, Chung HW¹.

Abstract

OBJECTIVES:

To evaluate preoperative anti-Müllerian hormone (AMH) levels in women with endometrioma or other benign ovarian cysts and differences of AMH changes according to various characteristics.

METHODS:

Ninety-seven patients aged 20 to 39 years who underwent surgery for benign ovarian cyst were enrolled retrospectively. Of these, 65 patients were diagnosed as endometriomas, and 32 had other benign cysts. Serum AMH, mean, maximum, and total diameter of ovarian cysts were measured. The AMH levels were compared according to pathology (endometrioma vs. other benign cyst), size of ovarian cyst, age-matched AMH quartile percentile and characteristics of endometrioma.

RESULTS:

Preoperative serum AMH level was significantly lower in endometrioma group than other benign cyst group (4.12 ± 2.42 ng/mL vs. 6.02 ± 2.29 ng/mL, P < 0.001). Serum AMH level was significantly lower in endometrioma group, especially in patients aged 30 to 39 years. Dividing to age-matched AMH quartile percentile, there were significantly fewer patients with AMH level ≥ 75 percentile in endometrioma group (24.6% vs. 50.0%, P = 0.035). Among 4 subgroups of endometrioma, patients with AMH level ≥ 75 percentile were significantly decreased in multiple bilateral endometrioma group. Mean and total diameter of cysts were negatively correlated with preoperative serum AMH level in other benign cyst group.

CONCLUSION:

We suggest that preoperative AMH level measurement might be considered in women with endometrioma, especially in 30 to 39 years old, multiple bilateral type, or big-sized other benign ovarian cyst to assess the diminished ovarian reserve.

 

 

Pathologe. 2016 Feb;37(1):84-7.

Tumor of the mesosalpinx with unclear differentiation.

Nann D¹, Gahlen S¹, Keul HG², Voigt HJ³, Fend F¹, Staebler A⁴.

 

Abstract

Female adnexal tumors of probable Wolffian origin (FATWO) are rare tumors, which are mostly localized in the broad ligament or the mesosalpinx. They show high intratumor and intertumor variability of histological patterns (e.g. solid, tubular, cribriform and cystic) with usually unremarkable cellular and nuclear morphology and a lower mitotic rate. In general, they behave in a benign fashion but there are rare cases with malignant transformation, so that careful examination and surveillance are necessary. Differential diagnoses include Sertoli-Leydig cell tumors, metastasized endometrioid carcinoma and the FATWO-like variant of the endometrioid carcinoma of the fallopian tubes. The FATWOs express pancytokeratin, CD10, vimentin, calretinin and inhibin A. Estrogen and progesterone receptors are expressed in a minority of cases, whereas epithelial membrane antigen (EMA) is not detectable.

 

 

Minerva Ginecol. 2016 Jun;68(3):352-63.

Laparoscopic power morcellation of presumed fibroids.

Brolmann HA¹, Sizzi O, Hehenkamp WJ, Rossetti A.

 

Abstract

Uterine leiomyoma is a highly prevalent benign gynecologic neoplasm that affects women of reproductive age. Surgical procedures commonly employed to treat symptomatic uterine fibroids include myomectomy or total or sub-total hysterectomy. These procedures, when performed using minimally invasive techniques, reduce the risks of intraoperative and postoperative morbidity and mortality; however, in order to remove bulky lesions from the abdominal cavity through laparoscopic ports, a laparoscopic power morcellator must be used, a device with rapidly spinning blades to cut the uterine tissue into fragments so that it can be removed through a small incision. Although the minimal invasive approach in gynecological surgery has been firmly established now in terms of recovery and quality of life, morcellation is associated with rare but sometimes serious adverse events. Parts of the morcellated specimen may be spread into the abdominal cavity and enable implantation of cells on the peritoneum. In case of unexpected sarcoma the dissemination may upstage disease and affect survival. Myoma cells may give rise to ‘parasitic’ fibroids, but also implantation of adenomyotic cells and endometriosis has been reported. Finally the morcellation device may cause inadvertent injury to internal structures, such as bowel and vessels, with its rotating circular knife. In this article it is described how to estimate the risk of sarcoma in a presumed fibroid based on epidemiologic, imaging and laboratory data. Furthermore the first literature results of the in-bag morcellation are reviewed. With this procedure the specimen is contained in an insufflated sterile bag while being morcellated, potentially preventing spillage of tissue but also making direct morcellation injuries unlikely to happen.

 

 

Gynecol Endocrinol. 2016 Jul;32(7):529-33.

The estrogen metabolites 2-methoxyestradiol and 2-hydroxyestradiol inhibit endometriotic cell proliferation in estrogen-receptor-independent manner.

Samartzis EP¹, Imesch P¹, Twiehaus A², Dubey RK², Leeners B².

 

Abstract

Endometriosis, a painful disorder associated with infertility, is estimated to occur in approximately 7-10% of reproductive age women. Although endometriosis is considered as an estrogen-dependent disease, the role of estrogen metabolites via receptor-independent mechanisms has not yet been comprehensively clarified. In the present study, growth studies were performed comparing the effect of estradiol (E2), estrogen metabolites, that is, 2-hydroxyestradiol (2-OHE2) and 2-methoxyestradiol (2-ME), as well as estrogen-receptor-independent mechanisms using the estrogen receptor antagonist fulvestrant, on cell proliferation of endometriotic cells. The estrogen metabolites 2-OHE2 and 2-ME inhibited cell growth in a dose-dependent manner in pharmacological doses. Lower concentrations of 2-OHE2 had a stimulating effect on cell proliferation while pharmacologic doses exerted an antimitogenic effect. The effects on cell growth were at least partially receptor-independent, as demonstrated by simultaneous receptor antagonization with fulvestrant. In conclusion, our results demonstrate that in pharmacological doses the estrogen metabolites 2-ME and 2-OHE2 show inhibiting effects on the proliferation of endometriotic cells and may be promising substances for the treatment of endometriosis.

 

 

J Genet Genome Res. 2015;2(2).

Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC).

Jim HS¹, Lin HY², Tyrer JP³, Lawrenson K⁴, Dennis J³, Chornokur G⁵, Chen Z², Chen AY², Permuth-Wey J⁵, Aben KK⁶, Anton-Culver H⁷, Antonenkova N⁸, Bruinsma F⁹, Bandera EV¹⁰, Bean YT¹¹, Beckmann MW¹², Bisogna M¹³, Bjorge L¹⁴, Bogdanova N¹⁵, Brinton LA¹⁶, Brooks-Wilson A¹⁷, Bunker CH¹⁸, Butzow R¹⁹, Campbell IG²⁰, Carty K²¹, Chang-Claude J²², Cook LS²³, Cramer DW²⁴, Cunningham JM²⁵, Cybulski C²⁶, Dansonka-Mieszkowska A²⁷, du Bois A²⁸, Despierre E²⁹, Sieh W³⁰, Doherty JA³¹, Dörk T¹⁵, Dürst M³², Easton DF³³, Eccles DM³⁴, Edwards RP³⁵, Ekici AB³⁶, Fasching PA³⁷, Fridley BL³⁸, Gao YT³⁹, Gentry-Maharaj A⁴⁰, Giles GG⁴¹, Glasspool R⁴², Goodman MT⁴³, Gronwald J²⁶, Harter P²⁸, Hasmad HN⁴⁴, Hein A¹², Heitz F²⁸, Hildebrandt MA⁴⁵, Hillemanns P¹⁵, Hogdall CK⁴⁶, Hogdall E⁴⁷, Hosono S⁴⁸, Iversen ES⁴⁹, Jakubowska A²⁶, Jensen A⁵⁰, Ji BT¹⁶, Karlan BY⁵¹, Kellar M¹¹, Kiemeney LA⁵², Krakstad C¹⁴, Kjaer SK⁵³, Kupryjanczyk J²⁷, Vierkant RA⁵⁴, Lambrechts D⁵⁵, Lambrechts S²⁹, Le ND⁵⁶, Lee AW⁴, Lele S⁵⁷, Leminen A⁵⁸, Lester J⁵¹, Levine DA¹³, Liang D⁵⁹, Lim BK⁶⁰, Lissowska J⁶¹, Lu K⁶², Lubinski J²⁶, Lundvall L⁴⁶, Massuger LF⁶³, Matsuo K⁴⁸, McGuire V⁶⁴, McLaughlin JR⁶⁵, McNeish I⁴², Menon U⁴⁰, Milne RL⁴¹, Modugno F⁶⁶, Thomsen L⁶⁷, Moysich KB⁵⁷, Ness RB⁶⁸, Nevanlinna H⁵⁸, Eilber U²², Odunsi K⁶⁹, Olson SH⁷⁰, Orlow I⁷⁰, Orsulic S⁵¹, Palmieri Weber R⁷¹, Paul J⁴², Pearce CL⁷², Pejovic T¹¹, Pelttari LM⁵⁸, Pike MC⁷³, Poole EM⁷⁴, Schernhammer E⁷⁵, Risch HA⁷⁶, Rosen B⁷⁷, Rossing MA⁷⁸, Rothstein JH³⁰, Rudolph A²², Runnebaum IB³², Rzepecka IK²⁷, Salvesen HB¹⁴, Schwaab I⁷⁹, Shu XO⁸⁰, Shvetsov YB⁸¹, Siddiqui N⁸², Song H⁴, Southey MC⁸³, Spiewankiewicz B⁸⁴, Sucheston-Campbell L⁵⁷, Teo SH⁸⁵, Terry KL⁸⁶, Thompson PJ⁴³, Tangen IL¹⁴, Tworoger SS⁷⁵, van Altena AM⁶³, Vergote I²⁹, Walsh CS⁵¹, Wang-Gohrke S²², Wentzensen N¹⁶, Whittemore AS³⁰, Wicklund KG⁷⁸, Wilkens LR⁸¹, Wu AH⁴, Wu X⁴⁵, Woo YL⁶⁰, Yang H¹⁶, Zheng W⁸⁷, Ziogas A⁷, Amankwah E⁸⁸, Berchuck A⁸⁹; Georgia Chenevix-Trench on behalf of the AOCS management group 95,96, Schildkraut JM⁹⁰, Kelemen LE⁹¹, Ramus SJ⁴, Monteiro AN⁵, Goode EL⁹², Narod SA⁹³, Gayther SA⁴, Pharoah PD⁹⁴, Sellers TA⁵, Phelan CM⁵.

 

Abstract

Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68-0.90, p = 5.59 × 10^-4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways.

 

 

Zhonghua Liu Xing Bing Xue Za Zhi. 2015 Sep;36(9):945-8

A cross-sectional study of infertility prevalence and influencing factors in Uygur and Kazak women, Xinjiang Uygur autonomous region.

Jiao Y¹, Song X¹, Cai X².

Abstract

OBJECTIVE:

To investigate the prevalence of infertility and related factors in Uygur and Kazak women in Xinjiang Uygur autonomous region (Xinjiang).

METHODS:

Questionnaire survey and pelvic examination were conducted among 535 Uygur women and 322 Kazak women at reproductive age who were selected through stratified cluster random sampling in Sansan and Fuhai counties in Xinjiang. The data were analyzed with software SPSS 17.0.

RESULTS:

The prevalence of infertility among the Uygur and Kazak women were 26.5% and 21.7% respectively, the difference was not statistically significant (P>0.05). The prevalence of primary infertility among the Uygur and Kazak women were 14.7%, and 8.7%, respectively, the difference was statistically significant (P<0.05). The prevalence of secondary infertility among the Uygur and Kazak women were 11.8% and 13.0%, respectively, the difference was not statistically significant (P>0.05). The prevalence of infertility in the Uygur women was correlated with household income, pelvic inflammation, endometriosis and BMI, while the prevalence of infertility in the Kazak women was correlated with age of marriage, endometriosis and the history of ectopic pregnancy.

CONCLUSION:

The prevalence of infertility was high among the Uygur and Kazak women at reproductive age in Xinjiang. The influencing factors varied with ethnic group. It is necessary to conduct targeted health education and provide early diagnosis and effective treatment.

 

 

Akush Ginekol (Sofiia). 2015;54(6):24-7.

LOCALIZATION AND SIZE OF THE LESIONS IN PELVIC ENDOMETRIOSIS.

Totev T, Tihomirova T, Tomov S, Gorchev G.

Abstract

OBJECTIVE:

The study aimed to describe localization and size of the lesions in pelvic endometriosis

MATERIAL AND METHODS:

A retrospective study was carried out including 375 patients with pelvic endometriosis who were operated in St. Marina Hospital-Pleven from January 2008 to July 2014.

RESULTS AND DISCUSSION:

The ovaries are the pelvic organs most affected (76%) by endometriosis, the lesions being usually 4-5 cm in size. Peritoneal endometriosis ranks second, with 58.2%, and the rarest is DIE with 0.5%.

CONCLUSION:

Localization, number and size of the endometriosis lesions determine the severity of the condition. These parameters are crucial for making decisions concerning the type and extent of surgical intervention.

 

 

 

 

 

Cytokine. 2017 Jan;89:229-234

p27kip1 overexpression regulates IL-1β in the microenvironment of stem cells and eutopic endometriosis co-cultures.

Gonçalves GA¹, Invitti AL², Parreira RM², Kopelman A², Schor E², Girão MJ³.

Author information

Abstract

Endometriosis is a gynecological benign chronic disease defined as the growth of endometrial glands and stroma in extra-uterine sites, most commonly implanted over visceral and peritoneal surfaces within the female pelvis causing inflammatory lesions. It affects around 10% of the female population and is often accompanied by chronic pelvic pain, adhesion formation and infertility. Therefore, endometriosis could be considered a “social disease”, since it affects the quality of life, reproductivity and also has a socio-economic impact. The expression of cell cycle and inflammatory proteins is modified in the endometriotic tissues. Immunostaining of glandular and stromal cells in endometrial biopsies obtained from patients with endometriosis compared with those of healthy control demonstrated that endometriotic tissues have lower levels of p27^kip1 protein. Endometriosis endometrial cells cultures have also lower levels of p27^kip1 compared to health endometrial cells cultures and restore the cell cycle balance when transduced with an adenoviral vector carring the p27^kip1 coding gene (Adp27EGFP). The low levels of p27^kip1 are related to the S phase in the cell cycle, whereas higher levels lead to a G1 cell cycle arrest. The inflammatory cytokine IL-1β was recently identified as another key protein in the endometriosis proliferation. This cytokine has elevated levels during the proliferative and secretory phases of the menstrual cycle. In endometriosisendometrial cells cultures the IL-1β stimulates the production of IL-6 and IL-8, increasing the cell proliferation and reducing the apoptosis and Bax expression in these cells. According to these remarks, this work aims to evaluate the inflammatory effects in vitro, but more next to what happens in a woman’s body, associating endometrial cells with stem cells, thus mimicking the endometrial microenvironment, with gene therapy using Adp27, notoriously known as controller cell cycle, apoptosis and potent modulator of VEGF expression.

 

 

Biol Reprod. 2016 Mar;94(3):60.

Synthetic Steroid Hormones Regulated Cell Proliferation Through MicroRNA-34a-5p in Human Ovarian Endometrioma.

Hsu CY¹, Hsieh TH², Tsai CF¹, Chen HS², Liang PI³, Hsu YL¹, Tsai EM⁴.

 

Abstract

Endometriosis is the hormone-dependent product of endometrial tissue found outside the uterus. Recently, micro-RNAs (miRNAs) were shown to play a role in endometriotic lesion development. However, the mechanism of steroid hormones responsible for miRNA remains obscure. In the present study, we assayed for the effects of synthetic steroid hormones (danazol, progesterone, and medroxyprogesterone acetate [MPA]) on miRNAs in endometriosis. We used a global miRNA expression profile microarray to evaluate miRNA expression in endometrial mesenchymal stem cells (EN-MSCs) of ovarian endometrioma following treatment with 1 μM danazol, progesterone, or MPA. Furthermore, we selected candidate miRNAs whose expression changed more than fivefold and compared the effects of danazol, progesterone, and MPA treatments and also compared those results with controls in EN-MSCs. Among those with a fivefold change, we found 13 ectopically upregulated miRNAs in EN-MSCs. To understand the function of these 13 miRNAs, we subjected their sequences to Ingenuity Pathway Analysis. According to both the etiology and pathogenesis of endometriosis, we found that miR-199a-5p and miR-34a-5p showed specific association with the disease, including molecular and cellular functions. Steroid hormone treatment elevated the levels of miR-199a-5p and miR-34a-5p. An inhibitor of miR-34a-5p also reduced the synthetic steroid hormones effects on cell proliferation. In vivo data revealed that miRNA levels in endometriotic lesions correlated with findings following in vitro synthetic hormone treatment. Our data show the effects of synthetic steroid hormones on miRNA regulation. These findings contribute to our understanding of the molecular impact of the synthetic steroid hormones and suggest a potential mechanism for endometriosis treatment.

 

 

J Cancer Sci Ther. 2015;7(7):258-265.

Comparative Analysis of Differentially Expressed miRNAs and their Downstream mRNAs in Ovarian Cancer and its Associated Endometriosis.

Wu RL¹, Ali S², Bandyopadhyay S¹, Alosh B¹, Hayek K¹, Daaboul MF¹, Winer I³, Sarkar FH⁴, Ali-Fehmi R¹.

Abstract

OBJECTIVE:

There is an increased risk of developing ovarian cancer (OC) in patients with endometriosis. Hence, development of new biomarkers may provide a positive clinical outcome for early detection. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in biological and pathological process and are currently used as diagnostic and prognostic markers in various cancers. In the current study, we assessed the differential expression of miRNAs from 19 paired ovarian cancer and its associated endometriosis tissue samples. In addition we also analyzed the downstream targets of those miRNAs.

METHODS:

Nineteen paired cases of ovarian cancer and endometriosis foci were identified by a gynecologic pathologist and macro-dissected. The total RNAs were extracted and subjected to comprehensive miRNA profiling from the pooled samples of these two different entities using microarray analysis. Later, the abnormal expressions of few selected miRNAs were validated in individual cases by quantitative real-time PCR (qRT-PCR). Ingenuity pathway analysis revealed target mRNAs which were validated by qRT-PCR.

RESULTS:

The miRNA profiling identified deregulation of greater than 1156 miRNAs in OC, of which the top seven were further validated by qRT-PCR. The expression of miR-1, miR-133a, and miR-451 were reduced significantly (p<0.0001) in the OC patients compared to its associated endometriosis. In contrast, the expression of miR-141, miR-200a, miR-200c, and miR-3613 were elevated significantly (p<0.05) in most of the OC patients. Furthermore, among the downstream mRNAs of these miRNAs, the level of PTEN expression was significantly (p<0.05) reduced in OC compared to endometriosis while no significant difference was observed in NF-κB expression.

CONCLUSION:

The expression of miRNAs and mRNAs in OC were significantly different compared to its concurrent endometriosis. These differential expressed miRNAs may serve as potential diagnostic and prognostic biomarkers for OC associated with endometriosis.

 

 

Nitric Oxide. 2016 Apr 1;54:15-29.

Dinitrosyl iron complexes with thiol-containing ligands as a “working form” of endogenous nitric oxide.

Vanin AF¹.

 

Abstract

The material presented herein is an overview of the results obtained by our research team during the many years’ study of biological activities and occurrence of dinitrosyl iron complexes (DNIC) with thiol-containing ligands in human and animal organisms. With regard to their dose dependence and vast diversity of biological activities, DNIC are similar to the system of endogenous NO, one of the most universal regulators of biological processes. The role of biologically active components in DNIC is played by their iron-dinitrosyl fragments, [Fe(NO)2], endowed with the ability to generate neutral NO molecules and nitrosonium ions (NO(+)). Their release is effected by heme-and thiol-containing proteins, which fulfill the function of biological targets and acceptors of NO and NO(+). Beneficial regulatory effects of DNIC on physiological and metabolic processes are numerous and diverse and include, among other things, lowering of arterial pressure and accelerated healing of skin wounds. In the course of fast decomposition of their Fe(NO)2 fragments (e.g., in the presence of iron chelators), DNIC produce adverse (cytotoxic) effects, which can best be exemplified by their ability to suppress the development of experimental endometriosis in animals. In animal tissues, DNIC with thiol-containing ligands are predominantly represented by the binuclear form, which, contrary to mononuclear DNIC detectable by the 2.03 signal, is EPR-silent. The ample body of evidence on biological activities and occurrence of DNIC gained so far clearly demonstrates that in human and animal organisms DNIC with thiol-containing ligands represent a “working form” of the system of endogenous NO responsible for its accumulation and stabilization in animal tissues as well as its further transfer to its biological targets.

Int J Clin Exp Pathol. 2015 Nov 1;8(11):15381-5.

Concurrent tamoxifen-related Müllerian adenofibromas in uterus and ovary.

Shi H¹, Chen X¹, Lv B¹, Zhang X¹.

 

Abstract

Tamoxifen is a widely used in anti-oestrogen treatment of breast cancer. Previous reports showed that tamoxifen is associated with proliferative endometrial lesions. We herein reported an unusual case of concurrent hyperplastic lesions in the uterine cavity and right ovary in a 45-year-old woman with tamoxifen therapy. Regular vaginal ultrasonography showed the progressive endometrial thickening and right ovary enlargement during the period of drug use. Both lesions in the uterine cavity and right ovary showed characteristics resembling that of Müllerian adenofibroma. There were also foci of endometriosis in her bilateral ovarian surfaces. We suggest that women taking tamoxifen with a known history of endometriosis should be followed with transvaginal ultrasonography periodically.

 

 

 

Minerva Ginecol. 2016 Oct;68(5):481-6.

Control-matched surgical evaluation of endometriosis progression after IVF: a retrospective cohort study.

Crochet P¹, Lathi RB, Dahan MH, Ocampo J, Nutis M, Nezhat CR.

Abstract

BACKGROUND:

The aim of this study was to examine the surgical findings at repeated surgeries for endometriosis and to compare disease progression in patients after IVF to those without interval fertility treatments.

METHODS:

A retrospective case-control study set at the referral center for gynecologic endoscopy at Stanford University. Women who had two surgeries for treatment of symptomatic endometriosis since 1997 were searched in the database. Twenty-one women were identified who underwent IVF treatment between the two procedures (IVF group), and compared to 36 women who did not receive any fertility treatment (controls). The main outcomes were time to recurrence and surgical findings including rASRM score. The presence and size of endometrioma, rectovaginal and para-rectal spaces location of endometriosis were also compared between the two surgical procedures.

RESULTS:

Demographics in the two groups were similar. The change in rASRM score between surgeries was not significantly different (P=0.80) between the two groups. There was no difference between the two groups in the size and number of pathology proven endometriomas as well as no difference in the presence of rectovaginal and pararectal endometriosis.

CONCLUSIONS:

No significant difference was found in the two groups, suggesting that IVF treatment does not lead to an accelerated progression of endometriosis in patients with recurrence.

 

 

 

Gynecol Oncol. 2016 Mar;140(3):481-5.

Comparing the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA): Two equivalent ways to differentiate malignant from benign ovarian tumors before surgery?

Yoshida A¹, Derchain SF¹, Pitta DR², Andrade LA³, Sarian LO⁴.

Abstract

AIM:

To evaluate the prediction of malignancy in women with pelvic masses using the Copenhagen Index (CPH-I) and Risk of Ovarian Malignancy Algorithm (ROMA).

PATIENTS AND METHODS:

Three hundred eighty four women operated due to an ovarian mass were enrolled between January 2010 and June 2015. All patients had histopathological diagnosis, HE4 and CA125 measurement. CPH-I and ROMA were calculated and their performances compared in two distinct scenarios: 1) for the discrimination of benign ovarian disease from epithelial ovarian cancer (EOC), non-epithelial ovarian cancer, borderline ovarian tumors (BOT) and ovarian metastases, and 2) for the discrimination of benign disease from EOC. Receiver Operator Characteristics’ Areas Under the Curves (AUC) were calculated for CPH-I and ROMA and compared.

RESULTS:

Of the 384 women, 224 presented a benign ovarian tumor, 32 BOT, 87 EOC, 26 non-epithelial ovarian cancer, and 15 had ovarian metastases. The best AUCs were obtained for the discrimination of EOC from benign tumors. CPH-I performed slightly better than ROMA, and both approached 89% sensitivity and 85% specificity. When all malignant tumors (EOC, BOT, ovarian metastases and non-epithelial ovarian cancer – entire cohort) were included, the performance of CPH-I and ROMA declined to nearly 72%, although the specificity remained close to 85%.

CONCLUSION:

CPH-I and ROMA performed similarly well for the discrimination of EOC from benign ovarian tumors. However, caution is necessary since, in practical situations, where all the histological possibilities for malignant ovarian tumors must be considered, the sensitivity of CPH-I and ROMA may not surpass 70%.