Front Biosci (Landmark Ed). 2014 Jun 1;19:1202-14.

Aberrant histone modification in endometriosis.

Nasu K1Kawano Y1Kai K1Aoyagi Y1Abe W1Okamoto M1Narahara H1.

 

Abstract

Accumulating evidence suggests that epigenetic aberrations play definite roles in the pathogenesis of endometriosis. These include aberrations in genomic DNA methylation, microRNA expression, and histone modification. The aberrant histone modification status and the aberrant expression of histone deacetylases, which regulate histone acetylation, in endometriosis are the focus of this review. Herein, we summarize the recent studies in the following areas: (i) hyperacetylation of histones located in the promoter lesions of G-protein-coupled estrogen receptor 1, steroidogenic factor-1, and hypoxia-inducible factor-1 alpha genes and (ii) hypoacetylation of histones located in the promoter lesions of estrogen receptor alpha, homeobox A10, CCAAT/enhancer-binding protein alpha, p16(INK4a), p21(Waf1/Cip1), p27(Kip1), checkpoint kinase 2, death receptor 6, and E-cadherin genes. Further research from the viewpoint of epigenetics may lead to the identification of the candidate molecules that are aberrantly expressed in endometriosis and may help elucidate the pathogenesis of this disease. In addition, epigenetic drugs (including histone deacetylase inhibitors) show promise for the treatment of endometriosis by amending the expression of these epigenetically dysregulated genes.

 

 

Pathologica. 2014 Mar;106(1):14-5.

A rare case of transmural endometriosis in primary adenocarcinoma of the rectum.

Falleni MBauer DOpocher EMoneghini LBulfamante GP.

 

Abstract

Intestinal endometriosis of the rectum and sigmoid colon, occurring in up to 34% of pelvic endometriosis, mimics a wide number of conditions that are difficult to differentiate from inflammatory or malignant diseases. Herein we report the first case of transmural endometriosis concomitant with advanced primary rectal adenocarcinoma, presenting with obstructive symptoms. Correct diagnosis based on morphological identification and immunohistochemical characterization of the two entities is crucial for treatment.

 

 

 

 

 

Am J Reprod Immunol. 2014 Oct;72(4):392-402.

The anti-inflammatory impact of omega-3 polyunsaturated Fatty acids during the establishment of endometriosis-like lesions.

Attaman JA1Stanic AKKim MLynch MPRueda BRStyer AK.

Abstract

PROBLEM:

The anti-inflammatory impact of three polyunsaturated fatty acids (3-PUFA) in endometriosis is incompletely understood. The effect of 3-PUFA on endometriosis-like lesions is evaluated as a potential anti-inflammatory treatment target.

METHOD OF STUDY:

Wild Type (WT) and transgenic Fat-1 mice (high levels of endogenous 3-PUFA) were utilized in a uterine tissue transplant endometriosis model. Experimental donor×host pairs included: WT×WT (WW), WT×Fat-1 (WF), and Fat-1×Fat-1 (FF). Cytokine content (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-17A, IFN-γ, TNF-γ, MCP-1 and RANTES) and immunocellular composition in lesions was determined.

RESULTS:

Intralesion IL-6 in WF hosts was 99-fold lower than WW hosts (P=0.03). Compared to WW host lesions, Cox-2 levels were decreased in WF [1.5-fold (P=0.02)] and FF [1.2-fold (P=0.01)] host lesions, respectively, and intralesion VEGF expression was increased [1.8-fold; P=0.02 (WF) and 1.5-fold; P=0.01 (FF)]. Lesions in FF hosts demonstrated reduced phosphohistone 3 expression (70%; P=0.03) compared to WW control hosts.

CONCLUSIONS:

Systemic host 3-PUFA levels influence immune, angiogenic, and proliferative factors implicated in the early establishment of endometriosis.

 

 

BMJ Case Rep. 2014 Jun 4;2014.

Management of pregnancy in woman with suspected malignant deep infiltrating endometriosis fistulised to the uterine cervix.

Richard F1Canlorbe G1Bazot M2Daraï E1.

 

Abstract

Deep infiltrating endometriosis (DIE) is a well-known cause of pelvic pain and infertility. Malignant transformation of DIE is rare but can be suggested by MRI. We report a case of a spontaneous pregnancy in a woman with suspicion of malignant transformation of DIE with fistulisation to the posterior uterine isthmus through to the cervical canal. The pregnancy was closely monitored and an uneventful caesarian section was performed at 34 weeks of gestation. This case raises the issue of the relevance of imaging techniques and management of pregnancy.

 

 

 

Biomed Res Int. 2014;2014:916212.

Power of proteomics in linking oxidative stress and female infertility.

Gupta S1Ghulmiyyah J1Sharma R1Halabi J1Agarwal A1.

 

Abstract

Endometriosis, PCOS, and unexplained infertility are currently the most common diseases rendering large numbers of women infertile worldwide. Oxidative stress, due to its deleterious effects on proteins and nucleic acids, is postulated to be the one of the important mechanistic pathways in differential expression of proteins and in these diseases. The emerging field of proteomics has allowed identification of proteins involved in cell cycle, as antioxidants, extracellular matrix (ECM), cytoskeleton, and their linkage to oxidative stress in female infertility related diseases. The aim of this paper is to assess the association of oxidative stress and protein expression in the reproductive microenvironments such as endometrial fluid, peritoneal fluid, and follicular fluid, as well as reproductive tissues and serum. The review also highlights the literature that proposes the use of the fertility related proteins as potential biomarkers for noninvasive and early diagnosis of the aforementioned diseases rather than utilizing the more invasive methods used currently. The review will highlight the power of proteomic profiles identified in infertility related disease conditions and their linkage with underlying oxidative stress. The power of proteomics will be reviewed with regard to eliciting molecular mechanisms for early detection and management of these infertility related conditions.

 

 

PLoS One. 2014 Jun 5;9(6):e97889.

Changes in expression pattern of selected endometrial proteins following mesenchymal stem cells infusion in mares with endometrosis.

Mambelli LI1Mattos RC2Winter GH2Madeiro DS3Morais BP3Malschitzky E4Miglino MA5Kerkis A3Kerkis I3.

 

Abstract

Mesenchymal stem cells (MSCs) due to their self-renewal potential and differentiation capacity are useful for tissue regeneration. Immunomodulatory and trophic properties of MSCs were demonstrated suggesting their use as medicinal signaling cells able to positively change local environment in injured tissue. Equine endometrosis is a progressive degenerative disease responsible for glandular alterations and endometrial fibrosis which causes infertility in mares. More precisely, this disease is characterized by phenotypic changes in the expression pattern of selected endometrial proteins. Currently, no effective treatment is available for endometrosis. Herein, we aimed at the evaluation of expression pattern of these proteins after allogeneic equine adipose tissue-derived multipotent mesenchymal stem cells (eAT-MSCs) infusion as well as at testing the capacity of these cells to promote endometrial tissue remodeling in mares with endometrosis. eAT-MSC (2 × 10(7)/animal) were transplanted into mares’ uterus and control animals received only placebo. Uterine biopsies were collected before (day 0) and after (days 7, 21 and 60) cells transplantation. Conventional histopathology as well as expression analysis of such proteins as laminin, vimentin, Ki-67-antigen, α-smooth muscle actin (α-SMA) and cytokeratin 18 (CK18) have been performed before and after eAT-MSCs transplantation. We demonstrated that eAT-MSCs induced early (at day 7) remodeling of endometrial tissue microenvironment through changes observed in intra cellular and intra glandular localization of aforementioned proteins. We demonstrated that eAT-MSCs were able to positively modulate the expression pattern of studied secretory proteins as well as, to promote the induction of glandular epithelial cells proliferation suggesting local benefits to committed endometrial tissue environment after eAT-MSCs transplantation.

 

 

Int J Gynecol Pathol. 2014 Jul;33(4):385-92.

A small organ takes center stage: selected topics in fallopian tube pathology.

Rutgers JK1Lawrence WD.

 

Abstract

In this paper we consider a number of non-neoplastic and neoplastic lesions of the fallopian tube. Emphasis has been placed on diagnostically difficult entities, some of which result in misdiagnosis and consequent alteration of treatment, including “pseudocarcinomas” that represent a florid epithelial response to acute and/or chronic salpingitis. Endometriosis-related lesions may cause infertility, or undergo malignant transformation to a Mullerian carcinoma, most frequently endometrioid and clear cell types. Pregnancy-related tubal lesions include the easily misdiagnosed metaplastic papillary tumor as well as several manifestations of ectopic pregnancy. Covered briefly are familial conditions such as the Peutz-Jeghers syndrome and its association with tubal mucinous metaplasia, clear cell papillary cystadenoma associated with von Hippel-Lindau syndrome, and the Li Fraumeni syndrome’s germline p53 mutation and its association with distal tubal p53 signatures. Miscellaneous tumors discussed include the common adenomatoid tumor and the uncommon female adnexal tumor of probable Wolffian origin. Important issues including the updated staging of fallopian tube carcinomas, and the histopathologic variants of endometrioid carcinomas and their sometimes unusual patterns that engender the potential for confusion with other tumors are briefly noted. The final section covers the relatively recent and novel concept of the fallopian tube as the predominant site of origin of ovarian and peritoneal carcinomas. Discussed are the histologic, immunohistochemical, and molecular biologic evidence that support the tubal fimbria as the site of serous tubal intraepithelial carcinoma, possibly the immediate precursor to high-grade ovarian and peritoneal serous carcinoma.

 

 

Int J Gynecol Pathol. 2014 Jul;33(4):393-401

Selected topics in peritoneal pathology.

Baker PM1Clement PBYoung RH.

 

Abstract

This essay considers selected peritoneal lesions many of which were the subject of studies coauthored by Dr Robert E. Scully. His article on multilocular peritoneal inclusion cysts has largely led to these lesions being considered non-neoplastic, eschewing the term cystic mesothelioma. These cysts are often associated with reactive mural mesothelial proliferations that can potentially lead to a misdiagnosis of mesothelioma. Clinical findings, such as a common association with endometriosis or prior operations, can prompt consideration of a reactive lesion. Mesothelial hyperplasia may be difficult to distinguish, when florid, from mesothelioma but a variety of gross and microscopic features will aid their recognition. Nodular peritoneal aggregates of histiocytes (sometimes admixed with mesothelial cells) may occasionally be a striking finding that can be misdiagnosed as a metastasis if the patient has a known neoplasm. Appreciation of their bland nuclear features and histiocytic nature, confirmed by immunohistochemical markers, facilitate the diagnosis. Various forms of peritonitis are briefly considered including sclerosing peritonitis, a process sometimes associated with luteinized thecomas (thecomatosis) of the ovaries, an entity first appreciated by Dr Scully. Mesotheliomas are briefly reviewed emphasizing the caution that should be used in applying the designation “well-differentiated papillary mesothelioma.” Many interpret the latter as benign, but multifocal lesions must be thoroughly examined histologically because of potential overlapping features with malignant mesothelioma. The morphologic spectrum of malignant mesothelioma and its usually straightforward distinction from müllerian neoplasms is considered, as is its occasional presentation as a dominant ovarian mass. The spectrum of low-grade serous peritoneal neoplasms including the “psammocarcinoma” is reviewed. Finally, various benign müllerian lesions, particularly endometriosis and endosalpingiosis, may be conspicuous in peritoneal specimens and sometimes are grossly striking. The usual presence of benign endometrioid epithelium and stroma should facilitate the correct diagnosis of endometriosis, but in cases in which the stroma is atrophic or the sole component (stromal endometriosis), diagnostic problems may arise.

 

 

Int J Gynecol Pathol. 2014 Jul;33(4):411-7.

The expression of Cox-2, NF-κB, and VEGF in ectopic endometrial tissues within fallopian tubes suggests different etiologies.

Tao X1Xie YWang LGu WYu XZhou X.

 

Abstract

The ectopic endometrial tissues lining the lumen of the fallopian tubes are currently defined as either “endometrial colonization” or “endometriosis” on the basis of their location within or beyond the isthmic portion of the fallopian tubes. The underlying etiology is unclear. The goal of this study was to define the fallopian endometrial lesions pathogenetically rather than anatomically. We investigated 39 cases of the ectopic endometrial tissues within the fallopian tubes, most of which exceeded the isthmus. Immunohistochemical analysis was performed to evaluate the expression of Cox-2, NF-κB, and VEGF, which are specifically expressed by classic endometriosis. Other clinicopathologic parameters were also recorded. The results indicated that the lesions that were confined to the mucosa might differ from those observed in the muscular or serosal layers, which showed significantly less surrounding inflammatory reaction and less concurrent salpingitis and other endometriotic lesions. The expression of Cox-2, NF-κB, and VEGF of the ectopic endometrial stromal cells tended to increase in the progression from the inner to the outer part of the tubes with significance. The expression of NF-κB and VEGF correlates with the microscopic findings of inflammation. Sterilization by tubal ligation exhibited a unique pattern of distribution. Except in those patients with tubal ligation, considering the different expression patterns observed in the tubal ectopic endometrial lesions, the mucosal type should be diagnosed as “endometrial colonization” wherever the lesion occurs. The others should be diagnosed as “endometriosis” to reveal the etiology identical to typical endometriotic lesions.

 

 

Acta Med Iran. 2014;52(5):341-4.

Histopathologic and sonographic analysis of laparoscopic removal ovarian nonendometriotic cyst: the evaluating effects on ovarian reserve.

Sarmadi S1Ahmadi FS1Ejtemaei Mehr S2Ghaseminejad A3Mohammad K4Nekuie S3Abbasi S5Karimi M4Gharibpoor F3Elahipanah Z6.

 

Abstract

Currently, laparoscopic cystectomy is the first-line therapy for ovarian benign cysts that are resistant to current therapies. There are different studies that point to ovarian reserve damage due to laparoscopic cystectomy. In this study, we evaluate the ovarian damage following laparoscopic cystectomy for non-endometriosis cysts using ultrasound and pathology findings. This is a prospective cohort study conducted between 7 rd month of 2011 and 10th month of 2012 in Women hospital affiliated to Tehran university of medical sciences.45 non-endometriosiscysts (17 teratoma,7 mucinous, 10 simple serous and 11 simple cysts) underwent laparoscopic cystectomy with stripping technique. Amount of excised parenchyma, number of lost oocytes and cyst wall fibrosis thickness were histopathologically studied. Before and 3 months after surgery antral follicle count was evaluated by ultrasound. AFC after cystectomy for teratoma and simple serous was significantly reduced P<0.05. By larger teratomas and more parenchyma inadvertently removed during their excision (1.64, 0.255) reduced AFC was seen and in simple serous cysts with more removed parenchyma amount (1.5) reduced AFC occurred. In our study simple cysts excision led to a loss in AFC that was not associated with any other cyst parameters. Mucinous cysts resection led to no specific ovarian reserve damage. Laparoscopic cystectomy for non-endometriosis leads to reduced ovarian reserve.

 

 

Schmerz. 2014 Jun;28(3):300-4.

Chronic pelvic pain in women.

Siedentopf F1Sillem M.

Abstract

BACKGROUND:

Chronic pelvic pain in women represents a difficult diagnostic and therapeutic problem in the gynecological practice which is always a challenge when dealing with affected women.

GYNECOLOGICAL CAUSES:

Possible gynecological causes are endometriosis, adhesions and/or pelvic inflammatory disease (PID), pelvic varicosis and ovarian retention syndrome/ovarian remnant syndrome. Other somatic causes are irritable bowel syndrome, bladder pain syndrome, interstitial cystitis and fibromyalgia.

PSYCHOSOCIAL FACTORS:

Psychosocial causes contributing to chronic pelvic pain are a high comorbidity with psychological factors, such as anxiety disorders and substance abuse or depression but the influence of social factors is less certain. The association with physical and sexual abuse also remains unclear.

DIAGNOSTICS AND THERAPY:

Important diagnostic steps are recording the patient history, a gynecological examination and laparoscopy. Multidisciplinary therapeutic approaches are considered to be very promising. Basic psychosomatic care and psychotherapy should be integrated into the therapeutic concept at an early stage.

 

 

Hum Reprod. 2014 Aug;29(8):1666-76.

A clinical score can predict associated deep infiltrating endometriosis before surgery for an endometrioma.

Lafay Pillet MC1Huchon C2Santulli P3Borghese B4Chapron C4Fauconnier A2.

Abstract

STUDY QUESTION:

Is it possible to detect associated deep infiltrating endometriosis (DIE) before surgery for patients operated on for endometriomas using a preoperative clinical symptoms questionnaire?

SUMMARY ANSWER:

A diagnostic score of DIE associated with endometriomas using four clinical symptoms defined a high-risk group where the probability of DIE was 88% and a low-risk group with a 10% probability of DIE.

WHAT IS KNOWN ALREADY:

Many clinical symptoms are already known to be associated with DIE but they have not yet been used to build a clinical prediction model.

STUDY DESIGN, SIZE, DURATION:

We built a diagnostic score of DIE based on a case control study of 326 consecutive patients operated on for an endometrioma between January 2005 and October 2011: 164 had associated DIE (DIE+) and 162 had no DIE (DIE-). We derived the score on a training sample obtained from a random selection of 2/3 of the population (211 patients, 101 DIE+, 110 DIE-), and validated the results on the remaining third (115 patients, 63 DIE+, 52 DIE-). The gold standard for the diagnosis of DIE was based on surgical exploration and histological diagnosis.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Participants were consecutive patients aged 18-42 years who underwent surgery for an endometrioma with histological confirmation and complete treatment of their endometriotic lesions: data for these women were extracted from a prospective database including a standardized preoperative questionnaire. On the training dataset, variables associated with DIE in a univariate analysis were introduced in a multiple logistic regression and selected by a backward stepwise procedure and a Jackknife procedure. A diagnostic score of DIE was built with the scaled/rounded coefficients of the multiple regression. Two cut-off values delimitated a high and a low risk group, and their diagnostic accuracy was tested on the validation dataset.

MAIN RESULTS AND THE ROLE OF CHANCE:

Four variables were independently associated with DIE: visual analogue scale of gastro-intestinal symptoms ≥5 or of deep dyspareunia >5 (adjusted diagnostic odds ratio (aDOR) = 6.0, 95% confidence interval (CI) [2.9-12.1]), duration of pain greater than 24 months (aDOR = 3.8, 95% CI [1.9-7.7]), severe dysmenorrhoea (defined as the prescription of the oral contraceptive pill for the treatment of a primary dysmenorrhoea or the worsening of a secondary dysmenorrhoea) (aDOR = 3.8, 95% CI [1.9-7.6]) and primary or secondary infertility (aDOR = 2.5, 95% CI [1.2-4.9]). The sum of these variables weighted by their rounded/scaled coefficients constituted the score ranging from 0 to 53. A score <13 defined a low-risk group where the probability of DIE was 10% (95% CI [7-15] with a sensitivity of 95% (95% CI [89-98]) and a negative likelihood ratio of 0.1 (95% CI [0.0-0.3]). A score ≥35 defined a high-risk group where the probability of DIE was 88% (95% CI [83-92%]), with a specificity of 94% (95% CI [87-97]), and a positive likelihood ratio of 8.1 (95% CI [3.9-17.0]). The performance of the score was confirmed on the validation dataset with 11% of DIE+ patients having a score <13 (sensibility: 95%) and 90% of DIE+ patients having a score ≥35 (specificity: 94%).

LIMITATION, REASONS FOR CAUTION:

This study was performed in a department specialized in DIE management. Score accuracy could be different in less specialized centres.

WIDER IMPLICATIONS OF THE FINDINGS:

This score could have a major clinical impact on the time of diagnosis, the management of DIE and could reduce the cost of investigations by helping to identify high-risk patients, while preserving the quality of care.

 

 

Hum Reprod. 2014 Aug;29(8):1688-97

Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol.

Broekmans FJ1Verweij PJ2Eijkemans MJ3Mannaerts BM2Witjes H2.

Abstract

STUDY QUESTION:

Can predictors of low and high ovarian responses be identified in patients undergoing controlled ovarian stimulation (COS) in a GnRH antagonist protocol?

SUMMARY ANSWER:

Common prognostic factors for high and low ovarian responses were female age, antral follicle count (AFC) and basal serum FSH and LH.

WHAT IS KNOWN ALREADY:

Predictors of ovarian response have been identified in GnRH agonist protocols. With the introduction of GnRH antagonists to prevent premature LH rises during COS, and the gradual shift in use of long GnRH agonist to short GnRH antagonist protocols, there is a need for data on the predictability of ovarian response in GnRH antagonist cycles.

STUDY DESIGN, SIZE, DURATION:

A retrospective analysis of data from the Engage trial and validation with the Xpect trial. Prognostic models were constructed for high (>18 oocytes retrieved) and low (<6 oocytes retrieved) ovarian response. Model building was based on the recombinant FSH (rFSH) arm (n = 747) of the Engage trial. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.15 for entry). Validation based on calibration was performed in patients with equivalent treatment (n = 199) in the Xpect trial.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Infertile women with an indication for COS prior to IVF. The Engage and Xpect trials included patients of similar ethnic origins from North America and Europe who had regular menstrual cycles. The main causes of infertility were male factor, tubal factor and endometriosis.

MAIN RESULTS AND THE ROLE OF CHANCE:

In the Engage trial, 18.3% of patients had a high and 12.7% had a low ovarian response. Age, AFC, serum FSH and serum LH at stimulation Day 1 were prognostic for both high and low ovarian responses. Higher AFC and LH were associated with an increased chance of high ovarian response. Older age and higher FSH correlated with an increased chance of low ovarian response. Region (North America/Europe) and BMI were prognostic for high ovarian response, and serum estradiol at stimulation Day 1 was associated with low ovarian response. The area under the receiver operating characteristic (ROC) curve (AUC) for the model for a high ovarian response was 0.82. Sensitivity and specificity were 0.82 and 0.73; positive and negative predictive values were 0.40 and 0.95, respectively. The AUC for the model for a low ovarian response was 0.80. Sensitivity and specificity were 0.77 and 0.73, respectively; positive and negative predictive values were 0.29 and 0.96, respectively. In Xpect, 19.1% of patients were high ovarian responders and 16.1% were low ovarian responders. The slope of the calibration line was 0.81 and 1.35 for high and low ovarian responses, respectively, both not statistically different from 1.0. In summary, common prognostic factors for high and low ovarian responses were female age, AFC and basal serum FSH and LH. Simple multivariable models are presented that are able to predict both a too low or too high ovarian response in patients treated with a GnRH antagonist protocol and daily rFSH.

LIMITATIONS, REASONS FOR CAUTION:

Anti-Müllerian hormone was not included in the prediction modelling.

WIDER IMPLICATIONS OF THE FINDINGS:

The findings will help with the identification of patients at risk of a too high or too low ovarian response and individualization of COS treatment.

STUDY FUNDING/COMPETING INTERESTS:

Financial support for this study and the editorial work was provided by Merck, Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA. F.J.B. received a grant from CVZ to his institution; P.J.M.V. and H.W. are employees of MSD, and B.M.J.L.M. was an employee of MSD at the time of development of this manuscript.

 

 

J Minim Invasive Gynecol. 2014 Nov-Dec;21(6):1086-90.

Co-existence of uterine myomas and endometriosis in women undergoing laparoscopic myomectomy: risk factors and surgical implications.

Maclaran K1Agarwal N1Odejinmi F2.

Abstract

STUDY OBJECTIVE:

To investigate the prevalence of and explore risk factors for the coexistence of uterine myomas and endometriosis and to assess operative outcomes during laparoscopic myomectomy.

DESIGN:

Retrospective cohort study (Canadian Task Force classification II-2).

SETTING:

Tertiary referral center in London, England.

PATIENTS:

Two hundred twelve women undergoing laparoscopic myomectomy to treat symptomatic uterine myomas.

INTERVENTION:

Laparoscopic myomectomy.

MEASUREMENTS AND MAIN RESULTS:

Coexisting myomas and endometriosis were identified in 21.2% of patients. Endometriosis was more common in those with subfertility (44% vs 25.7%; p = .02) and less common in those with bleeding disorders (20% vs 45%; p = .003). Parity, location of myoma, and race/ethnicity affected risk of endometriosis, whereas size and number of myomas did not. Of patients with endometriosis, 42% underwent surgical treatment of endometriosis during myomectomy. Significantly more patients with endometriosis also underwent ovarian cystectomy than did those without endometriosis (15.6% vs 3%; p = .004). Operative time was similar in both groups (109.6 minutes vs 116.4 minutes; p = .83), as was estimated blood loss (271 mL vs 327 mL; p = .16).

CONCLUSIONS:

A diagnosis of concomitant endometriosis should be considered, in particular in patients with subfertility and pain. This enables optimal preoperative counseling and consent for potential additional procedures such as treatment of endometriosis or ovarian cystectomy.

 

 

Gynecol Endocrinol. 2014 Sep;30(9):612-7.

Novel insights on the malignant transformation of endometriosis into ovarian carcinoma.

Gadducci A1Lanfredini NTana R.

 

Abstract

The malignant transformation of endometriosis is an uncommon event, which happens in 0.7-2.5% of the cases, and, when occurs, it usually involves the ovary. A 2 to 3-fold higher risk of ovarian endometrioid and clear cell carcinoma has been reported in women with endometriosis. Pathological studies have detected a morphological continuum of sequential steps from normal endometriotic cyst epithelium to atypical endometriosis and finally to invasive carcinoma. Ovarian endometrioid carcinoma harbors mutations of CTNNB1 in 16-53.3%, of PTEN in 14-20% and of ARID1A in 30-55% of the cases. Ovarian clear cell carcinoma harbors mutations of PIK3CA in 20-40% and of ARID1 in 15-75% of the cases. Whereas estrogen receptors and progesterone receptors are quite always absent, HNF-1b is often over-expressed in this histotype. Atypical endometriosis and endometriosis-related ovarian neoplasms share molecular alterations, such as PTEN mutations, ARID1A mutations and up-regulation of HNF-1b. Moreover, ARID1A mutations have been noted in clear cell tumors and contiguous atypical endometriosis, but not in distant endometriotic lesions. The loss of BAF250a protein expression is suggestive for the presence of ARID1A mutations, and represents an useful marker of malignant transformation of endometriosis.

 

 

Gynecol Endocrinol. 2014 Oct;30(10):726-9.

Efficacy of dienogest in the treatment of symptomatic adenomyosis: a pilot study.

Hirata T1Izumi GTakamura MSaito ANakazawa AHarada MHirota YKoga KFujii TOsuga Y.

 

Abstract

Adenomyosis is a common disorder in premenopausal women that causes dysmenorrhea, pelvic pain and menorrhagia. Considering that adenomyosis is an estrogen-dependent disease, the medical treatment is based on this hormone. Effective and well-tolerated medical treatments for symptomatic adenomyosis are needed. Dienogest, an oral progestin, has been extensively investigated in the treatment of endometriosis. In this report, we present the results on the efficacy and safety of dienogest in the treatment of symptomatic adenomyosis. Seventeen patients with symptomatic adenomyosis were included in this study, of which 15 continued dienogest for up to 24 weeks. Dienogest significantly reduced adenomyosis-associated pelvic pain as well as serum CA-125 and CA19-9 levels. It also demonstrated a modest suppression of estradiol (>50 pg/ mL), which is consistent with the findings of other reports. During treatment, five patients experienced worsening anemia because of metrorrhagia, which is the most frequent adverse effect associated with dienogest. This report suggests that dienogest is an effective and well-tolerated therapy for symptomatic adenomyosis.

 

 

J Am Soc Echocardiogr. 2014 Sep;27(9):1011-6.

Intracardiac leiomyomatosis: clinical findings and detailed echocardiographic features–a Chinese institutional experience.

Gu X1He Y1Li Z1Chen J1Liu W1Zhang Y1Nixon JV2.

Abstract

BACKGROUND:

Intravenous leiomyomatosis is a rare, benign, smooth muscle tumor originating in the uterus that may extend through the inferior vena cava into the heart. Intracardiac leiomyomatosis (ICL), present in 10% of patients with intravenous leiomyomatosis, may cause right heart failure, tricuspid valve obstruction, and pulmonary embolism. The imaging characteristics of ICL continue to be reported. The purposes of this study were to characterize the echocardiographic features of ICL and to correlate the clinical findings.

METHODS:

Between 1999 and 2012, 12 female patients with suspected ICL underwent cardiac surgery and histologic confirmation of the tumor. The clinical data, echocardiographic findings, and histologic results were retrospectively reviewed.

RESULTS:

The ages of the patients with ICL ranged from 40 to 59 years. Ten patients (83%) had undergone myomectomy or hysterectomy, one patient had a uterine fibroid, and one patient had endometriosis. Seven patients (58%) reported dyspnea and/or palpitations, and one patient had syncope; four patients were asymptomatic. Echocardiographic findings included six patients with homogenous right atrial masses, four patients with myxoma-like right atrial masses, and two patients with serpentine, convoluted right atrial masses. In nine patients, the right atrial masses were noted to cross the tricuspid valve. All masses extended from the inferior vena cava. No masses appeared to adhere to the right atrium, right ventricular or pulmonary arterial walls, or tricuspid valve. Tricuspid regurgitation was noted in all patients. No pulmonary emboli were present.

CONCLUSIONS:

The echocardiographic features of the ICL tumors varied. Tricuspid regurgitation and tumors emerging from the inferior vena cava were seen in all patients. Cardiac symptoms, including dyspnea, palpitations, and syncope, occurred in 67% of patients; the remaining 33% were asymptomatic.

 

 

Am J Pathol. 2014 Jul;184(7):1930-9.

A novel mouse model of endometriosis mimics human phenotype and reveals insights into the inflammatory contribution of shed endometrium.

Greaves E1Cousins FL2Murray A2Esnal-Zufiaurre A2Fassbender A3Horne AW2Saunders PT2.

 

Abstract

Endometriosis is an estrogen-dependent inflammatory disorder characterized by the presence of endometrial tissue outside the uterine cavity. Patients experience chronic pelvic pain and infertility, with the most likely origin of the tissue deposits (lesions) being endometrial fragments shed at menses. Menstruation is an inflammatory process associated with a dramatic increase in inflammatory mediators and tissue-resident immune cells. In the present study, we developed and validated a mouse model of endometriosis using syngeneic menstrual endometrial tissue introduced into the peritoneum of immunocompetent mice. We demonstrate the establishment of endometriotic lesions that exhibit similarities to those recovered from patients undergoing laparoscopy. Specifically, in both cases, lesions had epithelial (cytokeratin(+)) and stromal (vimentin/CD10(+)) cell compartments with a well-developed vasculature (CD31(+) endothelial cells). Expression of estrogen receptor β was increased in lesions compared with the peritoneum or eutopic endometrium. By performing experiments using mice with green fluorescent protein-labeled macrophages (MacGreen) in reciprocal transfers with wild-type mice, we obtained evidence that macrophages present in the peritoneum and in menses endometrium can contribute to the inflammatory microenvironment of the lesions. In summary, we developed a mouse model of endometriosis that exhibits similarities to human peritoneal lesions with respect to estrogen receptor expression, inflammation, and macrophage infiltration, providing an opportunity for further studies and the possible identification of novel therapies for this perplexing disorder.

 

Arch Gynecol Obstet. 2014 Nov;290(5):999-1006.

Atorvastatin exerts anti-nociceptive activity and decreases serum levels of high-sensitivity C-reactive protein and tumor necrosis factor-α in a rat endometriosis model.

Simsek Y1Gul MYilmaz EOzerol IHOzerol EParlakpinar H.

Abstract

PURPOSE:

The purpose of this study was to examine the effects of atorvastatin in the treatment of experimental endometriosis.

METHODS:

Endometriosis was induced in 24 female rats. 4 weeks after the procedure dimensions of the foci were recorded. Rats were divided into three groups: in Group 1 (n = 8), a daily dose of 10 mg/kg atorvastatin was given for 14 days. In the second group (n = 8), a single dose of 1 mg/kg leuprolide acetate was injected intraperitoneally. The rats in Group 3 (n = 8) were received 1 mg/kg i.p. 0.9 % NaCl. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriotic foci were recorded. Biochemical, histopathological and immunohistochemical studies were performed and nociception was compared in groups.

RESULTS:

Atorvastatin treatment exhibited significant analgesic activity in hot plate model (P = 0.022). The serum hs-CRP and tumor necrosis TNF-α levels were similar between the Group 2 and Group 3 (P > 0.05); however atorvastatin caused significant decrease in both serum markers. The histological and immunohistochemical scores were also found to be markedly lower in Group 1 and Group 2 (P < 0.05).

CONCLUSION:

Atorvastatin treatment may have a therapeutic potential in the treatment of endometriosisthrough its anti-inflammatory and anti-nociceptive properties.

 

 

World J Gastroenterol. 2014 Jun 7;20(21):6675-9.

Deep endometriosis with pericolic lymph node involvement: a case report and literature review.

Cacciato Insilla A1Granai M1Gallippi G1Giusti P1Giusti S1Guadagni S1Morelli L1Campani D1.

 

Abstract

Deep infiltrating endometriosis is an often-painful disorder affecting women during their reproductive years that usually involves the structures of the pelvis and frequently the gastrointestinal tract. We present the case of a 37-year-old female patient with an endometrial growth on the sigmoid colon wall causing pain, diarrhea and the presence of blood in the feces. The histology of the removed specimen also revealed the involvement of the utero-vesical fold, the recto-vaginal septum and a pericolic lymph node, which are all quite uncommon findings. To identify the endometrial cells, we performed immunohistochemical staining for CD10 and the estrogen and progesterone receptors.

 

 

Curr Opin Obstet Gynecol. 2014 Aug;26(4):290-4.

The benefits and challenges of robotic-assisted hysterectomy.

Smorgick N1As-Sanie S.

Abstract

PURPOSE OF REVIEW:

To analyze the recent evidence on robotic hysterectomy while highlighting its benefits and challenges.

RECENT FINDINGS:

Increased rates of robotic hysterectomy have led to decreasing rates of abdominal hysterectomy, after rates of the latter approach have been stagnant for many years. Robotic surgery has also the possible advantage of a relatively short learning curve, even though the case number required to reach proficiency may be actually closer to 100 cases. Recent studies comparing robotic and laparoscopic hysterectomy for benign indications have not demonstrated a clear advantage for either approach in terms of complications, blood loss, and hospital stay. The higher cost of robotic hysterectomy remains a significant disadvantage of this surgical approach, although the total cost may decrease with increasing surgeon’s experience (via shorter operative time) and may be offset in some circumstances by reduced hospital stay and cost of complications compared with abdominal hysterectomy.

SUMMARY:

The place of robotic hysterectomy in the gynecologic surgical armamentarium is still evolving. Although recent studies highlight the comparative outcomes of robotic and laparoscopic hysterectomy for benign cases, most surgeons are unlikely to be equally proficient in both techniques. Future studies will need to question whether subgroups of patients with complex benign disease such as endometriosis and pelvic adhesive disease may benefit from the robotic assistance.

 

 

 

Minerva Med. 2014 Aug;105(4):295-301.

Risk factors for recurrence rate of ovarian endometriomas following a laparoscopic cystectomy.

Moini A1Arabipoor AAshrafinia N.

Abstract

AIM:

Objective of the study was to evaluate the risk factors that influence the recurrence of endometrioma after laparoscopic excision.

METHODS:

A cross-sectional study was performed at Arash University Hospital between 2009 and 2011 on patients who had a minimum of one year of postoperative follow-up after undergoing a laparoscopic excision of an ovarian endometrioma. The patients had any prior surgery for ovarian endometriomas was excluded. Recurrence was defined as the presence of endometrioma more than 2 cm in size, detected by ultrasonography within 1 year of surgery. The variables including age at surgery, presence of infertility, uterine myoma, previous medical treatment of endometriosis, the size of the largest cyst at laparoscopy, unilateral or bilateral involvement, serum CA125 level, revised American Society for Reproductive Medicine (ASRM) score and stage, postoperative medical treatment and postoperative treatment were evaluated to assess their independent effects on the recurrence using logistic regression analysis.

RESULTS:

A total of 158 patients were admitted to the Surgery Unit for endometriomas cystectomy during the study period. After the initial assessment, 130 patients were eligible for the study. The overall rate of recurrence was 11.5% (15/130). Significant factors that were independently associated with higher recurrence were the size of the largest cyst (odds ratio [OR] =4, 95% confidence interval [95% CI] =1.6-10.4, P=0.002), a high rASRM score (OR=1.2, 95% CI=1-1.4, P=0.04) and woman age at surgery (OR=0.6, 95% CI=0.4-0.9, P=0.01).

CONCLUSION:

A high score of rASRM, large cyst size and young age at surgery were three significant factors that were associated with higher recurrence of endometriomas.

Tech Coloproctol. 2014 Nov;18(11):1099-104.

Ultrasonographic evaluation of anal endometriosis: report of four cases.

Kołodziejczak M1Sudoł-Szopińska ISantoro GABielecki KWiączek A.

Abstract

BACKGROUND:

The presence of endometriosis in the anal canal and perianal tissues is rare and difficult to suspect at clinical examination. We report our experience with preoperative ultrasound evaluation of four cases of anal endometriosis.

METHODS:

Four patients were evaluated by transperineal and high-resolution three-dimensional endoanal ultrasonography.

RESULTS:

In 3 of 4 women, the lesions involved old episiotomy scars. Anal endometriosis appeared as hypoechoic cystic lesions with areas of microcalcification, not well delimited and highly vascularized. The lesions either involved the anal sphincter (n = 2, one within the rectovaginal septum) or were localized superficially in the ischiorectal space (n = 2). Surgery and pathologic exam confirmed the ultrasonographic findings.

CONCLUSIONS:

Ultrasonographic findings of anal endometriosis are characteristics and may allow accurate preoperative staging of the disease.

 

 

Hum Reprod Update. 2014 Sep-Oct;20(5):737-47.

Central changes associated with chronic pelvic pain and endometriosis.

Brawn J1Morotti M2Zondervan KT3Becker CM3Vincent K3.

Abstract

BACKGROUND:

Chronic pelvic pain (CPP) is a significant public health problem with 1 million affected women in the UK. Although many pathologies are associated with CPP, the pain experienced is often disproportionate to the extent of disease identified and frequently no pathology is found (chronic pelvic pain syndrome). The central nervous system (CNS) is central to the experience of pain and chronic pain conditions in general are associated with alterations in both the structure and function of the CNS. This review describes the available evidence for central changes in association with conditions presenting with CPP.

METHODS:

A detailed literature search was performed to identify relevant papers, however, this is not a systematic review.

RESULTS:

CPP is associated with central changes similar to those identified in other pain conditions. Specifically these include, alterations in the behavioural and central response to noxious stimulation, changes in brain structure (both increases and decreases in the volume of specific brain regions), altered activity of both the hypothalamic-pituitary-adrenal axis and the autonomic nervous system (ANS) and psychological distress.

CONCLUSIONS:

The evidence reviewed in this paper demonstrates that CPP is associated with significant central changes when compared with healthy pain-free women. Moreover, the presence of these changes has the potential to both exacerbate symptoms and to predispose these women to the development of additional chronic conditions. These findings support the use of adjunctive medication targeting the CNS in these women.

 

 

Tuberc Respir Dis (Seoul). 2014 May;76(5):233-6.

A case of catamenial hemoptysis treated by bronchial artery embolization.

Shin SP1Park CY1Song JH1Kim HM1Min D1Lee SH1Kang SH1Jeon GS2Lee JH1.

 

Abstract

Catamenial hemoptysis is a rare condition, characterized by recurrent hemoptysis associated with the presence of intrapulmonary or endobronchial endometrial tissue. Therapeutic strategies proposed for intrapulmonary endometriosis with catamenial hemoptysis consist of medical treatments and surgery. Bronchial artery embolization is a well-established modality in the management of massive or recurrent hemoptysis, but has seldom been used for the treatment of catamenial hemoptysis. We report a case of catamenial hemoptysis associated with pulmonary parenchymal endometriosis, which was successfully treated by a bronchial artery embolization.

 

 

Curr Opin Obstet Gynecol. 2014 Aug;26(4):253-9.

Pain thresholds in women with chronic pelvic pain.

Giamberardino MA1Tana CCostantini R.

Abstract

PURPOSE OF REVIEW:

To update on the latest developments in sensory changes of female patients with chronic pelvic pain (CPP). CPP is very common, but its pathophysiology is still controversial. Evaluation of pain sensitivity in painful and nonpainful areas is key to understanding the underlying peripheral vs. central contributions to the symptom. This in turn is fundamental to improving the treatment strategies.

RECENT FINDINGS:

We reviewed the experimental studies published over the last year on pain thresholds to different stimuli measured at both the somatic and visceral level in women with different forms of recurrent or CPP. The majority of the studies indicate a pain threshold decrease to most stimuli in skin, subcutis and muscle in painful pelvic areas, the site of referred pain from pelvic viscera, as well as a decreased pain threshold in most viscera (colon and urinary bladder). A significant threshold decrease is also found in deep somatic tissues (subcutis and muscle) outside the painful zone in the most severe cases, indicating a state of central sensitization.

SUMMARY:

These findings have important implications for clinical practice: pain threshold measurement in both painful and nonpainful sites could have important predictive value of the clinical evolution and response to therapy of CPP.

 

 

Br J Pharmacol. 2014 Nov;171(21):4927-40.

Lipoxin A4 suppresses the development of endometriosis in an ALX receptor-dependent manner via the p38 MAPK pathway.

Wu R1Zhou WChen SShi YSu LZhu MChen QChen Q.

Abstract

BACKGROUND AND PURPOSE:

Lipoxins can function as endogenous ‘breaking signals’ in inflammation and play important roles in the progression of endometriosis. In this study, we further investigated the molecular mechanism by which lipoxin A4 (LXA4 ) suppresses the development of endometriosis.

EXPERIMENTAL APPROACH:

Primary endometriotic stromal cells (ESCs) were treated with IL-1β, or pre-incubated with LXA4 before incubation with IL-1β. The LXA4 receptor (ALX receptor) antagonist Boc-2 and gene-silencing approaches were used to study the involvement of the ALX receptor in anti-inflammatory signalling responses in ESCs. An animal model of endometriosis was induced in BALB/c mice by i.p. injection of an endometrium-rich fragment.

KEY RESULTS:

Decreased levels of LXA4 and 15-LOX-2 expression but increased expression of AXL receptors were observed in endometriotic tissues. LXA4 inhibited the release of inflammatory factors and phosphorylation of p38 MAPK in IL-1β-induced ESCs, an effect mediated by ALX receptors. LXA4 inhibited the proliferation of ESCs, as indicated by reduced DNA replication, caused G0 /G1 phase cell cycle arrest and down-regulated the expression of proliferating cell nuclear antigen in ESCs. LXA4 also attenuated the invasive activity of ESCs mainly by suppressing the expression and activity of MMP-9. In vivo, we further confirmed that LXA4 could inhibit the progression of endometriosis by acting as an anti-inflammatory.

CONCLUSIONS AND IMPLICATIONS:

LXA4 exerted anti-inflammatory, anti-proliferative and anti-invasive effects on endometriosis through a mechanism that involved down-regulating the activities of p38 MAPK, which was mediated by ALX receptors.

 

 

 

Zhonghua Yi Xue Za Zhi. 2014 Apr 22;94(15):1173-5.

Modified approach to difficult vaginal hysterectomy.

Li Y1Yang X2Cui Y2Huang S2Meng Q2Shen G2Wei F2Lü Q2Zhang Y2.

Abstract

OBJECTIVE:

To explore the advantage, feasibility and safety of modified approach to difficult vaginal hysterectomy and provide scientific rationales for expanding its indications.

METHODS:

A retrospective study was conducted for 237 patients undergoing hysterectomy for benign disease of uterus (without prolapse) from January 2009 to July 2012. Both modified approach to difficult vaginal hysterectomy (TVH, n = 167) and abdominal hysterectomy (TAH, n = 70) were performed. Two groups were compared for epidemiological, clinical characteristics, operative duration, intraoperative blood loss volume, perioperative and postoperative complications, hospitalization duration, inflammatory response and follow-up outcomes. TVH was divided into 3 subgroups of enlarged uterus (n = 100), prior pelvic surgeries/endometriosishistory (n = 25) and complicated cases with multiple factors (n = 42). Then the surgical outcome parameters were compared for each group.

RESULTS:

The operative duration, intraoperative blood loss volume and blood transfusion amount were significantly less in the TVH group than those in the TAH group (P < 0.05). No major perioperative complications occurred in either group. There was no conversion from TVH into TAH. Inflammatory response, gastrointestinal recovery and hospitalization duration for the TVH group were significantly shorter than those of the TAH group (P < 0.05). The hospitalization expense was almost the same in two groups (P > 0.05). Postoperative complications and the quality of sexual health were not statistically different between two groups at 1 month and 6 months post-operation (P > 0.05). The data of three TVH subgroups were collected. The complicated cases with multiple factors group had longer hospitalization duration than the enlarged uterus and the prior pelvic surgeries/endometriosis history groups (P < 0.05). Similarly the volume of blood loss in the complicated cases with multiple factors group was significantly more than those of other two groups (P < 0.05).

CONCLUSION:

As one kind of mini-invasive surgery with less complications, higher safety and feasibility, modified approach to difficult vaginal hysterectomy offers shorter operative duration, less volume of blood loss and faster recovery.

 

 

J Negat Results Biomed. 2014 Jun 12;13(1):12.

Lack of association between serotonin transporter 5-HTT gene polymorphism and endometriosis in an Italian patient population.

Megiorni F1Resta SYazdanian DCavaggioni GLia CBenedetti Panici PPizzuti APorpora MG.

Abstract

BACKGROUND:

The aim of this study was to determine whether the serotonin transporter gene (5-HTT), a key component in the control of the serotonergic system, is associated with endometriosis in an Italian population.

FINDINGS:

A case-control study, comprising 137 Italian patients with surgically confirmed endometriosis and 120 healthy controls, was carried out. 5-HTT genotypes (LL, SL and SS) were obtained by polymerase chain reaction and gel electrophoresis analysis. We found no overall difference in genotypic and allelic distributions of the 5-HTT gene between cases and controls.

CONCLUSIONS:

Our results suggest that the 5-HTT L/S promoter polymorphism is not associated with susceptibility to endometriosis in the studied Italian patients.

 

Gynecol Endocrinol. 2014 Oct;30(10):751-4.

Effects of long-term postoperative oral contraceptive use for the prevention of endometrioma recurrence on bone mineral density in young women.

Lee DY1Oh YKYoon BKChoi D.

 

Abstract

Concerns for negative effects of oral contraceptives (OCs) on bone mineral density (BMD) in long-term users have been raised, since OCs suppress the hypothalamic-pituitary-ovarian axis. However, there have been still limited data regarding the effects of long-term OC use on BMD in young women in the twenties. We investigated the effects of long-term OC use for the prevention of endometrioma recurrence on BMD in young women. Ninety-two women aged 20-30 years who underwent conservative surgery for endometrioma and used postoperative OC for at least 12 months to prevent the recurrence were included for this cross-sectional study, and BMDs after OC use were analyzed. The mean age at starting OC and duration of OC use was 25.6 ± 2.9 years and 40.7 ± 28.5 months, respectively. No correlation was found between BMDs and age at starting OC at all sites. In addition, BMDs were also not correlated with the duration of OC use, and were comparable according to the dose of OC (20 versus 30 μg). In conclusion, long-term use of OCs has no adverse effect on BMD in post-adolescent young women.

 

 

Immunol Invest. 2014;43(7):617-26.

IL-17A concentration of seminal plasma and follicular fluid in infertile men and women with various clinical diagnoses.

Sabbaghi M1Aram RRoustaei HFadavi Islam MDaneshvar MCastaño ARHaghparast A.

 

Abstract

Seminal plasma and follicular fluid (FF) cytokine analysis are valuable tools for diagnoses and validation of therapeutic approaches for improving the chance of conception. Despite the initial discovery over a decade ago, the IL-17 family has not received much attention in the case of infertility. In this study, we analyzed the level of IL-17A in seminal plasma, follicular fluid and blood serum of infertile patients with different clinical diagnoses by Enzyme Linked Immunosorbent Assay (ELISA). The results showed that the level of IL-17A was higher in seminal plasma and blood serum of varicocele patients than the control group. The level of this cytokine was higher in follicular fluid of endometriosis, polycystic ovary syndrome (PCOS) and tubal factor patients than the control group. A similar elevation in IL-17A level was observed in blood serum of these patients. Furthermore, there was a correlation between the numbers of meiosis I (MI) oocytes and the level of blood serum and follicular fluid IL-17A in PCOS patients. Our data suggest a putative role of IL-17A in mediating these conditions and may have possible applications in the development of more effective diagnostic tools and therapeutic treatments for human reproductive disorders.

 

 

Reprod Biol Endocrinol. 2014 Jun 13;12:50.

Molecular aspects of development and regulation of endometriosis.

Aznaurova YB1Zhumataev MBRoberts TKAliper AMZhavoronkov AA.

 

Abstract

Endometriosis is a common and painful condition affecting women of reproductive age. While the underlying pathophysiology is still largely unknown, much advancement has been made in understanding the progression of the disease. In recent years, a great deal of research has focused on non-invasive diagnostic tools, such as biomarkers, as well as identification of potential therapeutic targets. In this article, we will review the etiology and cellular mechanisms associated with endometriosis as well as the current diagnostic tools and therapies. We will then discuss the more recent genomic and proteomic studies and how these data may guide development of novel diagnostics and therapeutics. The current diagnostic tools are invasive and current therapies primarily treat the symptoms of endometriosis. Optimally, the advancement of “-omic” data will facilitate the development of non-invasive diagnostic biomarkers as well as therapeutics that target the pathophysiology of the disease and halt, or even reverse, progression. However, the amount of data generated by these types of studies is vast and bioinformatics analysis, such as we present here, will be critical to identification of appropriate targets for further study.

 

 

J Minim Invasive Gynecol. 2015 Jan;22(1):40-4.

Robotic-assisted laparoscopy vs conventional laparoscopy for the treatment of advanced stage endometriosis.

Nezhat CR1Stevens A2Balassiano E2Soliemannjad R2.

Abstract

STUDY OBJECTIVE:

To compare robotic-assisted laparoscopy with conventional laparoscopy for treatment of advanced stage endometriosis insofar as operative time, estimated blood loss, complication rate, and length of hospital stay.

STUDY DESIGN:

Retrospective cohort study (Canadian Task Force classification II2). All procedures were performed by one surgeon between January 2004 and July 2012. Data was collected via chart review.

SETTING:

Tertiary referral center for treatment of endometriosis.

PATIENTS:

Four hundred twenty women with advanced endometriosis.

INTERVENTIONS:

Fertility-sparing surgery to treat advanced endometriosis, either via conventional or robotic-assisted laparoscopy.

MEASUREMENTS AND MAIN RESULTS:

Patient demographic data, operative time, estimated blood loss, complication rate, and length of hospital stay were compared between the 2 groups. Two hundred seventy-three patients underwent conventional laparoscopy and 147 patients underwent robotic-assisted laparoscopy for fertility-sparing treatment of advanced stage endometriosis. Patients in both groups had similar characteristics insofar as age, body mass index, and previous abdominal surgeries. There were no significant differences in blood loss or complication rate between the 2 groups. Mean operative time in the conventional laparoscopy group was 135 minutes (range, 115-156 minutes), and in the robotic-assisted laparoscopy group was 196 minutes (range, 185-209 minutes), with a mean difference in operative time of 61 minutes (p < .001). Length of hospital stay was also significantly increased in the robotic-assisted laparoscopy group. Most patients who underwent conventional laparoscopy were discharged to home on the day of surgery. Of 273 patients in the conventional laparoscopy group, only 63 remained in the hospital overnight, and all 147 patients in the robotic-assisted laparoscopy group were discharged on postoperative day 1.

CONCLUSION:

Conventional laparoscopy and robotic-assisted laparoscopy are excellent methods for treatment of advanced stages of endometriosis. However, use of the robotic platform may increase operative time and might also be associated with longer hospital stay.

 

 

J Minim Invasive Gynecol. 2015 Jan;22(1):45-9.

Single-port (OctoPort) assisted extracorporeal ovarian cystectomy for the treatment of large ovarian cysts: compare to conventional laparoscopy and laparotomy.

Chong GO1Hong DG1Lee YS2.

Abstract

STUDY OBJECTIVE:

To evaluate single-port assisted extracorporeal cystectomy for treatment of large ovarian cysts and to compare its surgical outcomes, complications, and cystic content spillage rates with those of conventional laparoscopy and laparotomy.

DESIGN:

Retrospective study (Canadian Task Force classification II-2).

SETTING:

University teaching hospital.

PATIENTS:

Twenty-five patients who underwent single-port assisted extracorporeal cystectomy (group 1), 33 patients who underwent conventional laparoscopy (group 2), and 25 patients who underwent laparotomy (group 3).

INTERVENTIONS:

Surgical outcomes, complications, and spillage rates in group 1 were compared with those in groups 2 and 3.

MEASUREMENTS AND MAIN RESULTS:

Patients characteristics and tumor histologic findings were similar in the 3 groups. The mean (SD) largest diameter of ovarian cysts was 11.4 (4.2) cm in group 1, 9.7 (2.3) cm in group 2, and 12.0 (3.4) cm in group 3. Operative time in groups 1 and 2 was similar at 69.3 (26.3) minutes vs 73.1 (36.3) minutes (p = .66); however, operative time in group 1 was shorter than in group 3, at 69.3 (26.3) minutes vs 87.5 (26.6) minutes (p =.02). Blood loss in group 1 was significantly lower than in groups 2 and 3, at 16.0 (19.4) mL vs 36.1 (20.7) mL (p < .001) and 16.0 (19.4) mL vs 42.2 (39.7) mL (p = .005). The spillage rate in group 1 was profoundly lower than in group 2, at 8.0% vs 69.7% (p < .001).

CONCLUSION:

Single-port assisted extracorporeal cystectomy offers an alternative to conventional laparoscopy and laparotomy for management of large ovarian cysts, with comparable surgical outcomes. Furthermore, cyst content spillage rate in single-port assisted extracorporeal cystectomy was remarkably lower than that in conventional laparoscopy.

 

 

 

 

 

 

Eur J Med Chem. 2014 Jul 23;82:394-406.

Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker.

Abdelsamie AS1Bey E2Hanke N2Empting M3Hartmann RW4Frotscher M5.

 

Abstract

Estradiol is the most potent estrogen in humans. It is known to be involved in the development and proliferation of estrogen dependent diseases such as breast cancer and endometriosis. The last step of its biosynthesis is catalyzed by 17β-hydroxysteroid dehydrogenase type 1 (17β- HSD1) which consequently is a promising target for the treatment of these diseases. Recently, we reported on bicyclic substituted hydroxyphenylmethanones as potent inhibitors of 17β-HSD1. The present study focuses on rational structural modifications in this compound class with the aim of gaining more insight into its structure-activity relationship (SAR). (4-Hydroxyphenyl)-(5-(3-hydroxyphenylsulfanyl)-thiophen-2-yl)methanone (25) was discovered as a member of a novel potent class of human 17β-HSD1 inhibitors. Computational methods were used to elucidate its interactions with the target protein. The compound showed activity also towards the murine 17β-HSD1 enzyme and thus is a starting point for the design of compounds suitable for evaluation in an animal disease model.

 

 

J Minim Invasive Gynecol. 2015 Mar-Apr;22(3):378-83.

External validation of the SF-36 quality-of-life questionnaire in Italian and Brazilian populations to select patients with colorectal endometriosis for surgery.

Laas E1Zacharopoulou C1Montanari G2Seracchioli R2Abrão MS3Bassi MA3Ballester M1Daraï E4.

Abstract

STUDY OBJECTIVE:

To evaluate the external validity of the validated French model of the quality-of-life questionnaire (QOL) SF-36 in predicting improvement after colorectal resection for endometriosis.

DESIGN:

Italian and Brazilian cohort studies (Canadian Task Force classification II-3).

SETTING:

Tertiary referral university hospital in Brazil and expert center in endometriosis in Italy.

PATIENTS:

Patients with colorectal endometriosis from an Italian population (n = 63) and a Brazilian population (n = 151).

INTERVENTION:

Laparoscopic colorectal resection for treatment of endometriosis.

MEASUREMENTS AND MAIN RESULTS:

Preoperative and postoperative evaluations of the Physical Component Summary (PCS) and the Mental Component Summary (MCS) of the SF-36 were performed. Substantial improvement in PCS and MCS was observed after colorectal resection in both populations. In the Brazilian population, the receiver operating curve (ROC) (area under the curve [AUC]) was 0.83 (95% confidence interval [CI], 0.77-0.89) for MCS and 0.78 (95% CI, 0.71-0.83) for PCS, demonstrating good discrimination performance. The mean difference between the predicted and calibrated probabilities was 19.6% for MCS and 32.8% for PCS. In the Italian population, the ROC curve (AUC) was 0.65 (95% CI, 0.52-0.78) for PCS and 0.67 (95% CI, 0.55-0.78) for MCS. The model demonstrated poor discrimination and calibration performance for PCS (p < .001) and MCS (p = .003). The mean difference between the predicted and calibrated probabilities was 17.5% for MCS and 21.8% for PCS.

CONCLUSION:

Despite the use of validated translations of the SF-36, our results underline the limits of this tool in selection of patients for colorectal resection due to underestimation of predicted quality of life, possibly because of variations in epidemiologic characteristics of the populations.

 

 

Reprod Biol Endocrinol. 2014 Jun 16;12:51.

Blood soluble interleukin 1 receptor accessory protein levels are consistently low throughout the menstrual cycle of women with endometriosis.

Michaud NAl-Akoum MAkoum A1.

Abstract

BACKGROUND:

A deficiency in the counter-regulatory mechanisms of interleukin 1 (IL1) may play a significant role in endometriosis pathogenesis and associated chronic inflammation. The aim of this study was to investigate peripheral blood levels of soluble IL1 receptor accessory protein (sIL1RAP), a potent natural inhibitor of IL1, in women with and without endometriosis.

METHODS:

Peripheral blood samples were collected from women with endometriosis (n = 47) consulting for infertility, pelvic pain or tubal ligation, in whom the disease was diagnosed at laparoscopy. Control healthy women (n = 27) were requesting tubal ligation or reanastomosis and had no visible evidence of endometriosis at laparoscopy. sIL1RAP levels were determined by ELISA, whereas estradiol (E2) and progesterone (P4) levels were determined by competitive immunoassays.

RESULTS:

sIL1RAP levels were significantly decreased in women with early endometriosis stages compared to controls (p < 0.05) and markedly during the proliferative phase of the menstrual cycle (p < 0.001). Actually, while sIL1RAP were significantly increased in the proliferative compared to the secretory phase in normal women (p < 0.0001) and peaked at the end of this phase, sIL1RAP remained consistently low and showed non-significant variations throughout the menstrual cycle in women with endometriosis.

CONCLUSIONS:

Lower circulating levels of sIL1RAP points to a significant impairment in the counter-regulatory mechanisms of IL1, which in view of the cytokine’s potent inflammatory and growth-promoting properties may play a significant role in the pathophysiology of endometriosis.

 

 

Oman Med J. 2014 May;29(3):226-31.

Endometriosis after surgical menopause mimicking pelvic malignancy: surgeons’ predicament.

Bhat RA1Teo M2Bhat AK3.

 

Abstract

Prevalence of persistent endometriosis in women after menopause without any hormonal replacement therapy is very rare. This is a case of a woman with previous history of total hysterectomy and bilateral salpingo-oophorectomy for endometriosis who presented with hemoperitoneum, vaginal bleeding, pelvic mass, and pulmonary thromboembolism mimicking as rectovaginal septum carcinoma. This is the first case report with a unique mode of presentation wherein the patient presented with hemoperitoneum requiring emergency embolization of the vessel to stabilize the patient. She underwent en bloc resection of the tumor with high anterior resection of the rectum. Histopathology confirmed endometriosis.

 

 

 

Oman Med J. 2014 May;29(3):239-41.

Clinical and histological profile of surgically managed benign adnexal masses.

Gowri V1Al Shukri M1Al Khaduri M1Machado L1.

Abstract

OBJECTIVE:

To study the clinical and histological nature of benign adnexal masses managed surgically.

METHODS:

A retrospective descriptive study in a teaching hospital in Oman of all the women who had surgical management of benign adnexal masses from January 2008 to May 2012. Data pertaining to age, parity, presenting symptoms, imaging and tumor markers performed and the surgical intervention done on those women with benign adnexal masses was collected from the electronic health records of the patients.

RESULTS:

There were 198 women during this period operated for benign adnexal masses. The most common benign neoplasm was mature teratoma of the ovary followed by endometriosis. Conservative surgery in the form of ovarian cystectomy was necessary in three fourths of women and in about just less than 50% of women, the procedure was completed laparoscopically.

CONCLUSION:

The most common benign tumor was teratoma but laparoscopic approach, which is the standard of care in these women, was possible only in just about 50% of the women.

 

 

PLoS One. 2014 Jun 17;9

miR-451 deficiency is associated with altered endometrial fibrinogen alpha chain expression and reduced endometriotic implant establishment in an experimental mouse model.

Nothnick WB1Graham A1Holbert J1Weiss MJ2.

 

Abstract

Endometriosis is defined as the growth of endometrial glandular and stromal components in ectopic locations and affects as many as 10% of all women of reproductive age. Despite its high prevalence, the pathogenesis of endometriosis remains poorly understood. MicroRNAs, small non-coding RNAs that post-transcriptionally regulate gene expression, are mis-expressed in endometriosis but a functional role in the disease pathogenesis remains uncertain. To examine the role of microRNA-451 (miR-451) in the initial development of endometriosis, we utilized a novel mouse model in which eutopic endometrial fragments used to induce endometriosis were deficient for miR-451. After induction of the disease, we evaluated the impact of this deficiency on implant development and survival. Loss of miR-451 expression resulted in a lower number of ectopic lesions established in vivo. Analysis of differential protein profiles between miR-451 deficient and wild-type endometrial fragments revealed that fibrinogen alpha polypeptide isoform 2 precursor was approximately 2-fold higher in the miR-451 null donor endometrial tissue and this elevated expression of the protein was associated with altered expression of the parent fibrinogen alpha chain mRNA and protein. As this polypeptide contains RGD amino acid “cell adhesion” motifs which could impact early establishment of lesion development, we examined and confirmed using a cyclic RGD peptide antagonist, that endometrial cell adhesion and endometriosisestablishment could be respectively inhibited both in vitro and in vivo. Collectively, these results suggest that the reduced miR-451 eutopic endometrial expression does not enhance initial establishment of these fragments when displaced into the peritoneal cavity, that loss of eutopic endometrial miR-451 expression is associated with altered expression of fibrinogen alpha chain mRNA and protein, and that RGD cyclic peptide antagonists inhibit establishment of endometriosis development in an experimental mouse model suggesting that this approach may prove useful in the prevention of endometriosis establishment and survival.

 

 

Br J Cancer. 2014 Aug 12;111(4):680-8.

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study.

Testa A1Kaijser J2Wynants L3Fischerova D4Van Holsbeke C5Franchi D6Savelli L7Epstein E8Czekierdowski A9Guerriero S10Fruscio R11Leone FP12Vergote I13Bourne T14Valentin L15Van Calster B16Timmerman D2.

Abstract

BACKGROUND:

To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3.

METHODS:

This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery.

RESULTS:

The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5.

CONCLUSIONS:

This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.

 

 

J Reprod Med. 2014 May-Jun;59(5-6):330-2.

Clear cell adenocarcinoma of the abdominal wall: a case report.

Heller DSHouck KLee ESGranick MS.

Abstract

BACKGROUND:

Primary clear cell adenocarcinoma of the abdominal wall is exceptionally rare and most likely arises within scar endometriosis.

CASE:

A 37-year-old woman with 3 prior cesarean sections developed an abdominal wall mass that was confirmed as clear cell adenocarcinoma.

CONCLUSION:

Clear cell adenocarcinoma is in the differential diagnosis of abdominal wall masses, particularly in cases of prior surgery. Fine needle aspiration may be helpful in establishing the diagnosis.

 

 

Mol Hum Reprod. 2014 Sep;20(9):905-18.

Menstrual blood-derived stromal stem cells from women with and without endometriosis reveal different phenotypic and functional characteristics.

Nikoo S1Ebtekar M2Jeddi-Tehrani M3Shervin A1Bozorgmehr M4Vafaei S4Kazemnejad S5Zarnani AH6

Abstract

Retrograde flow of menstrual blood cells during menstruation is considered as the dominant theory for the development of endometriosis. Moreover, current evidence suggests that endometrial-derived stem cells are key players in the pathogenesis of endometriosis. In particular, endometrial stromal stem cells have been suggested to be involved in the pathogenesis of this disease. Here, we aimed to use menstrual blood, as a novel source of endometrial stem cells, to investigate whether stromal stem cells from endometriosis (E-MenSCs) and non-endometriosis (NE-MenSCs) women differed regarding their morphology, CD marker expression pattern, proliferation, invasion and adhesion capacities and their ability to express certain immunomodulatory molecules. E-MenSCs were morphologically different from NE-MenSCs and showed higher expression of CD9, CD10 and CD29. Furthermore, E-MenSCs had higher proliferation and invasion potentials compared with NE-MenSCs. The amount of indoleamine 2,3-dioxygenase-1 (IDO1) and cyclooxygenase-2 (COX-2) in E-MenSCs co-cultured with allogenic peripheral blood mononuclear cells (PBMCs) was shown to be higher both at the gene and protein levels, and higher IDO1 activity was detected in the endometriosis group. However, NE-MenSCs revealed increased concentrations of forkhead transcription factor-3 (FOXP3) when compared with E-MenSCs. Nonetheless, interferon (IFN)-γ, Interleukin (IL)-10 and monocyte chemoattractant protein-1 (MCP-1) levels were higher in the supernatant of E-MenSCs-PBMC co-cultures. Here, we showed that there are inherent differences between E-MenSCs and NE-MenSCs. These findings propose the key role MenSCs could play in the pathogenesis of endometriosis and further support the retrograde and stem cell theories of endometriosis. Hence, considering its renewable and easily available nature, menstrual blood could be viewed as a reliable and inexpensive material for studies addressing the cellular and molecular aspects of endometriosis.

 

 

Hum Reprod. 2014 Aug;29(8):1730-8.

Expression of the transmembrane mucins, MUC1, MUC4 and MUC16, in normal endometrium and in endometriosis.

Dharmaraj N1Chapela PJ1Morgado M1Hawkins SM2Lessey BA3Young SL4Carson DD5.

Abstract

STUDY QUESTION:

Are the transmembrane mucins, MUC1, MUC4 and MUC16, differentially expressed in endometriosis compared with normal endometrium?

SUMMARY ANSWER:

This study revealed that transmembrane mucin expression does not vary significantly in normal endometrium during the menstrual cycle and is not altered in endometriosis relative to the epithelial marker, cytokeratin-18 (KRT18).

WHAT IS KNOWN ALREADY:

Increased serum levels of the transmembrane mucin fragments MUC1, MUC4 and MUC16 that normally dominate the apical surface of simple epithelia are found in several pathological conditions, including endometriosis. Altered mucin expression in gynecologic diseases may promote infertility or endometrial pathologies.

STUDY DESIGN, SIZE, DURATION:

This was a laboratory-based study of samples from 12 endometriosispatients as well as non-endometriosis control samples obtained from 31 patients.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Total RNA was isolated from endometrial biopsies of ectopic and eutopic endometrium from women with endometriosis and control patients from different stages of the menstrual cycle. Quantitative (q)-RT-PCR analyses were performed for the mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, cytokeratin-18 (KRT18), or β-actin (ACTB). Frozen sections from endometrial biopsies of proliferative and mid-secretory stage women with endometriosis were immunostained for MUC1, MUC4 and MUC16.

MAIN RESULTS AND THE ROLE OF CHANCE:

qRT-PCR analyses of MUC1 and MUC16 mRNA revealed that these mucins do not vary significantly during the menstrual cycle nor are they altered in women with endometriosis relative to the epithelial marker, KRT18. MUC4 mRNA is expressed at very low levels relative to MUC1 and MUC16 under all conditions. There was little difference in MUC1 and MUC16 expression between eutopic endometrial and ectopic endometriotic tissues. MUC4 expression also was not significantly higher in the ectopic endometriotic tissues. Immunostaining for all three mucins reveals robust expression of MUC1 and MUC16 at the apical surfaces of endometrial epithelia, but little to no staining for MUC4.

LIMITATIONS, REASONS FOR CAUTION:

qRT-PCR analysis was the main method used for mucin detection. Additional studies with stage III-IV endometriotic tissue would be useful to determine if changes in MUC1 and MUC16 expression occur, or if MUC4 expression increases, at later stages of endometriosis.

WIDER IMPLICATIONS OF THE FINDINGS:

We report a comprehensive comparative profile of the major transmembrane mucins, MUC1, MUC4 and MUC16, relative to the epithelial marker, KRT18, in normal cycling endometrium and in endometriosis, and indicate constitutive expression. Previous studies have profiled the expression of individual mucins relative to β-actin and indicate accumulation in the luteal phase. Thus, these differences in interpretation appear to reflect the increased epithelial content of endometrium during the luteal phase.

 

 

 

BJOG. 2014 Dec;121(13):1653-8.

Transverse vaginal septae: management and long-term outcomes.

Williams CE1Nakhal RSHall-Craggs MAWood DCutner APattison SHCreighton SM.

Abstract

OBJECTIVE:

To examine the management and long-term outcomes of transverse vaginal septae.

DESIGN:

Observational study with cross-sectional and retrospective arms.

SETTING:

Tertiary referral centre specialising in Müllerian anomalies.

POPULATION:

Forty-six girls and women with a transverse vaginal septum.

METHODS:

Data from medical records of all cases (1998-2013) of transverse vaginal septae were collected and reviewed. Patients over 16 years of age also completed a questionnaire.

MAIN OUTCOME MEASURES:

Presentation, examination findings, investigations, surgery, and long-term reproductive outcomes.

RESULTS:

The septae in the study were described as follows: 61% (95% CI 0.46-0.74) were imperforate, and presented with obstructed menstruation; 39% (95% CI 0.26-0.54) were perforate, and presented with a variety of concerns; 72% (95% CI 0.57-0.83) were low, 22% (95% CI 0.12-0.36) were mid-vaginal, and 6% (95% CI 0.02-0.18) were high; 33% were managed via an abdominoperineal approach, 59% were managed via a vaginal approach, and 6% had laparoscopic resection (one patient did not have surgery); 11% (95% CI 0.05-0.23) of patients presented with reobstruction, all following abdominoperineal vaginoplasty; 7% presented with vaginal stenosis, two following vaginal resection and one following the abdominoperineal approach; 61% of questionnaires were returned. These results showed that 22/23 patients were menstruating and one had a hysterectomy, 74% had been sexually active, 35% had dyspareunia, and 36% complained of dysmenorrhoea. There were seven pregnancies, with one termination and six live births, all following the vaginal excision of a transverse vaginal septum.

CONCLUSIONS:

Transverse vaginal septae resected vaginally or laparoscopically have low complication rates and good long-term outcomes. Complex septae require more extensive surgery, with an increased risk of complications.

 

Int J Surg Pathol. 2015 Apr;23(2):140-3.

Clear cell adenocarcinoma arising in an adenomyoma of the broad ligament.

Torres D1Parker L2Moghadamfalahi M2Sanders MA2Metzinger DS2.

 

Abstract

Extrauterine adenomyomas are extremely rare benign tumors of smooth muscles, endometrial glands, and endometrial stroma. Ectopic endometrial glands can undergo malignant change. The ovary is the most common site of malignant change in endometriosis. Cancer arising in extraovarian endometriosis is a rare event with limited cases in the literature. To the best of our knowledge, we present the first case of a clear cell adenocarcinoma arising from foci of ectopic endometrial tissue in an adenomyoma of the broad ligament. It supports the association between endometriomas and clear cell adenocarcinoma. Therefore, patients with a significant history of endometriosis may benefit from close follow-up or definitive surgery.

 

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