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Pag. 22

J Minim Invasive Gynecol. 2012 Jan-Feb;19(1):46-51. Epub 2011 Nov 16.

Endometriosis of the round ligament of the uterus.

Crispi CP, de Souza CA, Oliveira MA, Dibi RP, Cardeman L, Sato H, Schor E.


Fernandes Figueira Institute-FIOCRUZ, Rio de Janeiro, Brazil.



To demonstrate the prevalence of endometriosis in the intrapelvic portion of the round ligaments of the uterus (RLUs) and to propose criteria for their excision.


Retrospective case series analysis of women undergoing laparoscopy for the treatment of deep infiltrating endometriosis (Canadian Task Force classification II-3).


Tertiary referral hospital.


We evaluated 174 patients who underwent laparoscopy for the treatment of deep infiltrating endometriosis (DIE) between April 2006 and May 2009.


All patients underwent laparoscopy for the treatment of DIE and had their RLUs removed when there was shortening, deviation, or thickening. After removal, the RLUs were sent for histopathologic analysis to verify the presence or absence of endometriosis.


The prevalence of endometriosis in the RLUs and the association between the macroscopic alterations and the anatomic pathology results were determined. After the identification of macroscopic alterations, 1 or both RLUs (for a total of 42) were removed from 27 of the 174 patients who underwent laparoscopy. The positive predictive value (PPV) of the macroscopic criteria proposed for endometriosis of the RLU was 83.3% (95% confidence interval [CI] = 72.1%-94.5%), with 35 positive RLUs out of the 42 that were excised. The prevalence of endometriosis of the RLU was 13.8% (95% CI = 8.7%-18.9%), with 24 patients having a positive histopathologic examination result for endometriosis.


The prevalence of RLU endometriosis in patients with DIE was 13.8%, which emphasizes that a rigorous evaluation of this structure must be part of the routine surgical treatment of patients with endometriosis.

J Obstet Gynaecol Res. 2012 Jan;38(1):9-15. doi: 10.1111/j.1447-0756.2011.01685.x. Epub 2011 Nov 9.

Laparoscopic management of large ovarian tumors: clinical tips for overcoming common concerns.

Hong JH, Choi JS, Lee JH, Son CE, Jeon SW, Bae JW.


Department of Obstetrics and Gynecology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.



This study was performed to assess the feasibility and efficacy of laparoscopic management for patients with large ovarian tumors.


A retrospective analysis was performed of the medical records of 52 women who underwent laparoscopic surgery for large ovarian tumors whose maximum diameter was ≥15cm and a low possibility of malignancy.


The median age of patients was 35years (range 18-84), median body mass index was 22.4kg/m(2) (range 12.4-31.5) and 18 patients had previous operative history. The median tumor diameter was 17cm (range 15-40). There were no conversions to laparotomy and perioperative complications. The median operating time, estimated blood loss, and hospital stay were 80min (range 25-225), 100mL (range 50-500) and 3days (range 2-14), respectively. The operative procedures performed were salpingo-oophorectomy (n=26), ovarian cystectomy (n=16), laparoscopically assisted vaginal hysterectomy with unilateral or bilateral salpingo-oophorectomy (n=9), and laparoscopically assisted staging surgery (n=1). The histopathological results were mucinous cystadenoma (n=25), mature cystic teratoma (n=9), serous cystadenoma (n=6), endometrioma (n=5), mucinous borderline tumor (n=4), follicular cyst (n=2), and clear cell carcinoma (n=1).


Laparoscopic management of large ovarian tumors is feasible and efficient with appropriate patient selection and experience of surgeons.

J Radiol Case Rep. 2012;6(3):9-15. Epub 2012 Mar 1.

Herlyn-Werner-Wunderlich syndrome: a rare presentation with pyocolpos.

Cox D, Ching BH.


Department of Radiology, Tripler Army Medical Center, Honolulu, HI, USA.


Obstructed hemivagina and ipsilateral renal anomaly (OHVIRA), also known as Herlyn-Werner-Wunderlich syndrome, is a rare syndrome with only a few hundred reported cases described since 1922. Only a handful of these cases have been associated with pyocolpos. Mullerian duct anomalies have an incidence of 2-3%. While OHVIRA constitutes 0.16-10% of these Mullerian duct anomalies. Symptoms usually present shortly after menarche when hematocolpos develops during menstruation resulting in dysmenorrhea and a pelvic mass. The pelvic mass is the collection of blood products within the obstructed hemivagina. The first study in the diagnostic work-up is usually ultrasonography, which typically demonstrates a pelvic fluid collection which can simulate other disease processes thus confounding the diagnosis. MRI findings of the pelvis reveal a didelphic uterus. Imaging of the abdomen reveals agenesis of the ipsilateral kidney. MRI is beneficial in characterizing the didelphic uterus and vaginal septum for pre-operative planning. Understanding the imaging findings, in conjunction with the clinical presentation, is critical for early diagnosis in attempting to prevent complications such as endometriosis or adhesions from chronic infections with subsequent infertility.

J Radiol Case Rep. 2012;6(1):25-30. Epub 2012 Jan 1.

Thoracic endometriosis: a case report.

Chatra PS.


Department of Radiology, Yenepoya Medical College, Deralakatte, Mangalore, India.


Thoracic endometriosis is a rare form of extrapelvic endometriosis. These patients typically present with catamenial pneumothorax or hemoptysis. Adequate clinical history coupled with HRCT helps in early diagnosis and appropriate management of thoracic endometriosis.

J Reprod Immunol. 2012 Jan;93(1):58-63. Epub 2011 Dec 29.

The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. II: adenomyosis and macrophages.

Tremellen KP, Russell P.


Repromed, Adelaide, Australia. ktremellen@repromed.com.au


Adenomyosis, a condition usually associated with multiparity, is not generally seen as a cause of infertility. However, recent studies have reported a reduction in IVF implantation rates and a link with miscarriage, suggesting that adenomyosis may interfere with successful implantation. To investigate this hypothesis, the clinical records and laboratory results, which routinely include immunohistochemical examination of a late luteal phase endometrial biopsy for leukocytes, were retrospectively reviewed for 64 women with implantation failure and who previously had been screened for the presence of adenomyosis by pelvic MRI. The presence of either diffuse or “adenomyoma” type of adenomyosis was associated with a marked increase (p=0.004) in the density of macrophages and natural killer cells in the endometrial stroma, compared to those women with mild focal adenomyosis or no disease. These findings point to an immunological mechanism by which adenomyosis might interfere with successful embryo implantation.

J Reprod Med. 2012 Jan-Feb;57(1-2):81-4.

Can ovariopexy at the end of surgery for endometriosis be recommended? A case report.

Daraï E, Touboul C, Ballester M, Poncelet C.


Department of Gynecology-Obstetrics, Hôpital Tenon, Université Pierre et Marie Curie, Paris. emile.darai@tnn.aphp.fr



Endometriosis affects 10-15% of the female population in the reproductive period and is detected in up to 40% of infertile women. Surgery is indicated to improve fertility and symptoms in these women, but some patients experience severe complications and develop postoperative adhesion. We discuss the potential impact on adhesion of systematic ovariopexy at the end of surgery for endometriosis.


We report a case of a 31-year-old woman who underwent initial laparoscopic removal of endometriomas and rectovaginal endometriosis with bilateral transient ovariopexy five years ago. She was referred for recurrence of symptoms and infertility. Preoperative transvaginal sonography and MRI confirmed the recurrence of endometriosis with bilateral uterosacral ligament and rectal involvement. At laparoscopy severe and dense adhesions of the ovaries to the anterior abdominal wall using nonabsorbable suture were observed associated with distortion of tubal anatomy. In addition to the removal of these adhesions, a sigmoid adhesiolysis was performed with uterosacral ligament, rectosigmoid and vaginal resections, followed by a systematic protective colostomy.


This case illustrates the deleterious impact on adhesions to the abdominal wall of transient ovariopexy at the end of surgery for endometriosis.

Med Hypotheses. 2012 Jan;78(1):134-5. Epub 2011 Nov 4.

Cervicitis associated with lateral cervical displacement.

Gjoni I, Muneyyirci-Delale O.


Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, SUNY Downstate Medical Center, Kings County Hospital Center, 450 Clarkson Avenue, Box 24, Brooklyn, NY 11203, United States.


Lateral cervical displacement has been recognized as a sign of endometriosis; however, other causes of the finding have not been explored. In our experience, patients without endometriosis are presenting with lateral cervical displacement, mainly towards the left of midline. The common finding in these cases is the presence of cervicitis leading us to hypothesize the role of cervicitis in causing lateral displacement of the cervix. Future research into this area will provide us with a stronger understanding of the role that lateral cervical displacement plays in the development of pelvic pathology and the development of cervical cancer.

Published by Elsevier Ltd.

Mod Pathol. 2012 Jan;25(1):122-30. doi: 10.1038/modpathol.2011.143. Epub 2011 Oct 7.

Accumulative copy number increase of MET drives tumor development and histological progression in a subset of ovarian clear-cell adenocarcinomas.

Yamamoto S, Tsuda H, Miyai K, Takano M, Tamai S, Matsubara O.


Department of Basic Pathology, National Defense Medical College, Tokorozawa, Japan.


Our previous study demonstrated that, among ovarian carcinomas, amplification of the MET gene and overexpression of MET specifically and commonly occur in clear-cell adenocarcinoma histology. This study was conducted to address how these alterations contribute to development and progression of this highly chemoresistant form of ovarian cancer. We histologically reviewed 21 previously described MET amplification-positive clear-cell adenocarcinoma cases, and selected 11 tumors with synchronous endometriosis and 2 tumors with adjacent clear-cell adenofibroma (CCAF) components. Using double in situ hybridization and immunohistochemistry, copy number alterations of the MET gene and levels of MET protein expression were analyzed in these putative precursor lesions and the corresponding invasive carcinoma components in this selected cohort. All of the non-atypical precursor lesions analyzed (ie, non-atypical endometrioses and the benign CCAFs) were negative for MET gain. However, low-level (≥3 MET copies in ≥10% and ≥4 MET copies in 10-40% of tumor cells) gain of MET was detected in 4 (40%) of the 10 atypical endometrioses and 1 of the 2 borderline CCAFs. Moreover, high-level (≥4 MET copies in ≥40% of tumor cells) gain of MET were detected in five (50%) of the atypical endometrioses. In 4 (31%) of the 13 cases enrolled, intratumoral heterogeneity for MET gain was documented in invasive carcinoma components, wherein all the relatively differentiated carcinoma components showed low-level gain of MET and all the corresponding poorly differentiated carcinomas showed high-level gain. The overall incidence of MET overexpression gradually increased from the precursors of non-atypical form (0%), through those of atypical form (67%) and the relatively differentiated carcinoma components (92%), to the poorly differentiated carcinoma components (100%). These results suggest that accumulative MET gene copy number alterations causing MET overexpression are associated with higher tumor grade and might drive the development and progression of the MET amplification-positive ovarian clear-cell adenocarcinoma.

Obstet Gynecol Int. 2012;2012:786132. Epub 2011 Dec 26.

Infertility and adenomyosis.

Campo S, Campo V, Benagiano G.


Institute of Obstetrics and Gynaecology, Catholic University of Sacred Heart, Largo Agostino Gemelli, 00168 Roma, Italy.


Classically, the diagnosis of adenomyosis has only been possible on a hysterectomy specimen, usually in women in their late fourth and fifth decades, and, therefore, evaluating any relationship with infertility was simply not possible. As a consequence, to this day, no epidemiologic data exists linking adenomyosis to a state of subfertility. Today, new imaging techniques have enabled a noninvasive diagnosis at a much earlier time and a number of single-case or small series reports have appeared showing that medical, surgical, or combined treatment can restore fertility in women with adenomyosis, an indirect proof of an association. At the functional level, several anomalies found in the so-called junctional zone, or inner myometrium, in adenomyosis patients have been shown to be associated with poor reproductive performance, mainly through perturbed uterine peristalsis. Additional evidence for an association comes from experimental data: in baboons, adenomyosis is associated with lifelong primary infertility, as well as to endometriosis. Finally, indirect proof comes from studies of the eutopic and ectopic endometrium in women with adenomyosis proving the existence of an altered endometrial function and receptivity. In conclusion, sufficient indirect proof exists linking adenomyosis to infertility to warrant systematic clinical studies.

Obstet Gynecol Int. 2012;2012:561306. Epub 2011 Nov 29.

Cornual polyps of the fallopian tube are associated with endometriosis and anovulation.

Alasiri SA, Ghahremani M, McComb PF.


Division of Reproductive Endocrinology & infertility, Department of Obstetrics and Gynaecology, Faculty of Medicine, BC Women’s Hospital and Women’s Health Centre, The University of British Columbia, Vancouver, BC, Canada V6H 3N1.


Background. The relationship between tubal cornual polyps and endometriosis and ovulatory disorders in infertile women is unclear. Our objective was to determine such an association from our database and review the literature. Methods. Twenty-two infertile women with tubal cornual polyps were assessed for coexistence of oligoovulation/anovulation and endometriosis with stratification for polyp diameter (large: ≥5 mm diameter, small <5 mm diameter). Result(s). Oligoovulation/anovulation was more prevalent in women with large versus small tubal cornual polyps (P = 0.0048). Endometriosis was associated with both large and small polyps. Conclusion(s). This case series confirms the association of tubal cornual polyps with oligoovulation/anovulation and endometriosis in infertile women. This case series is limited by a lack of controls.

PLoS One. 2012;7(5):e37750. Epub 2012 May 25.

Angiotensin II Activates the Calcineurin/NFAT Signaling Pathway and Induces Cyclooxygenase-2 Expression in Rat Endometrial Stromal Cells.

Abraham F, Sacerdoti F, De León R, Gentile T, Canellada A.


Instituto de Estudios de la Inmunidad Humoral “Profesor Ricardo A. Margni” (CONICET-UBA), Cátedra de Inmunología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.


Cyclooxygenase (COX)-2, the inducible isoform of cyclooxygenase, plays a role in the process of uterine decidualization and blastocyst attachment. On the other hand, overexpression of COX-2 is involved in the proliferation of the endometrial tissue during endometriosis. Deregulation of the renin-angiotensin-system plays a role in the pathophysiology of endometriosis and pre-eclampsia. Angiotensin II increases intracellular Ca(2+) concentration by targeting phospholypase C-gamma in endometrial stromal cells (ESC). A key element of the cellular response to Ca(2+) signals is the activity of the Ca(2+)- and calmodulin-dependent phosphatase calcineurin. Our first aim was to study whether angiotensin II stimulated Cox-2 gene expression in rat ESC and to analyze whether calcineurin activity was involved. In cells isolated from non-pregnant uteri, COX-2 expression -both mRNA and protein- was induced by co-stimulation with phorbol ester and calcium ionophore (PIo), as well as by angiotensin II. Pretreatment with the calcineurin inhibitor cyclosporin A inhibited this induction. We further analyzed the role of the calcineurin/NFAT signaling pathway in the induction of Cox-2 gene expression in non-pregnant rat ESC. Cyclosporin A abolished NFATc1 dephosphorylation and translocation to the nucleus. Cyclosporin A also inhibited the transcriptional activity driven by the Cox-2 promoter. Exogenous expression of the peptide VIVIT -specific inhibitor of calcineurin/NFAT binding- blocked the activation of Cox-2 promoter and the up-regulation of COX-2 protein in these cells. Finally we analyzed Cox-2 gene expression in ESC of early-pregnant rats. COX-2 expression -both mRNA and protein- was induced by stimulation with PIo as well as by angiotensin II. This induction appears to be calcineurin independent, since it was not abrogated by cyclosporin A. In conclusion, angiotensin II induced Cox-2 gene expression by activating the calcineurin/NFAT signaling pathway in endometrial stromal cells of non-pregnant but not of early-pregnant rats. These results might be related to differential roles that COX-2 plays in the endometrium.

PLoS One. 2012;7(5):e37264. Epub 2012 May 23.

Macrophage migration inhibitory factor antagonist blocks the development of endometriosis in vivo.

Khoufache K, Bazin S, Girard K, Guillemette J, Roy MC, Verreault JP, Al-Abed Y, Foster W, Akoum A.


Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d’Assise, CHUQ, Quebec City, Québec, Canada.


Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and ß3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential therapeutic avenue.

PLoS One. 2012;7(5):e36776. Epub 2012 May 11.

MGEx-Udb: A Mammalian Uterus Database for Expression-Based Cataloguing of Genes across Conditions, Including Endometriosis and Cervical Cancer.

Bajpai AK, Davuluri S, Chandrashekar DS, Ilakya S, Dinakaran M, Acharya KK.


Institute of Bioinformatics and Applied Biotechnology (IBAB), Bengaluru (Bangalore), Karnataka State, India.



Gene expression profiling of uterus tissue has been performed in various contexts, but a significant amount of the data remains underutilized as it is not covered by the existing general resources.


We curated 2254 datasets from 325 uterus related mass scale gene expression studies on human, mouse, rat, cow and pig species. We then computationally derived a ‘reliability score’ for each gene’s expression status (transcribed/dormant), for each possible combination of conditions and locations, based on the extent of agreement or disagreement across datasets. The data and derived information has been compiled into the Mammalian Gene Expression Uterus database (MGEx-Udb, http://resource.ibab.ac.in/MGEx-Udb/). The database can be queried with gene names/IDs, sub-tissue locations, as well as various conditions such as the cervical cancer, endometrial cycles and disorders, and experimental treatments. Accordingly, the output would be a) transcribed and dormant genes listed for the queried condition/location, or b) expression profile of the gene of interest in various uterine conditions. The results also include the reliability score for the expression status of each gene. MGEx-Udb also provides information related to Gene Ontology annotations, protein-protein interactions, transcripts, promoters, and expression status by other sequencing techniques, and facilitates various other types of analysis of the individual genes or co-expressed gene clusters.


In brief, MGEx-Udb enables easy cataloguing of co-expressed genes and also facilitates bio-marker discovery for various uterine conditions.

PLoS One. 2012;7(4):e35535. Epub 2012 Apr 20.

IL-6 and mouse oocyte spindle.

Banerjee J, Sharma R, Agarwal A, Maitra D, Diamond MP, Abu-Soud HM.


Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, United States of America. jbanerje@med.wayne.edu


Interleukin 6 (IL-6) is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL) for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001) as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.

PLoS One. 2012;7(3):e33241. Epub 2012 Mar 22.

Towards endometriosis diagnosis by gadofosveset-trisodium enhanced magnetic resonance imaging.

Schreinemacher MH, Backes WH, Slenter JM, Xanthoulea S, Delvoux B, van Winden L, Beets-Tan RG, Evers JL, Dunselman GA, Romano A.


Department of Surgery, Maastricht University and Medical Centre, Maastricht, The Netherlands.


Endometriosis is defined as the presence of endometrial tissue outside the uterus. It affects 10-15% of women during reproductive age and has a big personal and social impact due to chronic pelvic pain, subfertility, loss of work-hours and medical costs. Such conditions are exacerbated by the fact that the correct diagnosis is made as late as 8-11 years after symptom presentation. This is due to the lack of a reliable non-invasive diagnostic test and the fact that the reference diagnostic standard is laparoscopy (invasive, expensive and not without risks). High-molecular weight gadofosveset-trisodium is used as contrast agent in Magnetic Resonance Imaging (MRI). Since it extravasates from hyperpermeable vessels more easily than from mature blood vessels, this contrast agent detects angiogenesis efficiently. Endometriosis has high angiogenic activity. Therefore, we have tested the possibility to detect endometriosis non-invasively using Dynamic Contrast-Enhanced MRI (DCE-MRI) and gadofosveset-trisodium as a contrast agent in a mouse model. Endometriotic lesions were surgically induced in nine mice by autologous transplantation. Three weeks after lesion induction, mice were scanned by DCE-MRI. Dynamic image analysis showed that the rates of uptake (inwash), persistence and outwash of the contrast agent were different between endometriosis and control tissues (large blood vessels and back muscle). Due to the extensive angiogenesis in induced lesions, the contrast agent persisted longer in endometriotic than control tissues, thus enhancing the MRI signal intensity. DCE-MRI was repeated five weeks after lesion induction, and contrast enhancement was similar to that observed three weeks after endometriosis induction. The endothelial-cell marker CD31 and the pericyte marker α-smooth-muscle-actin (mature vessels) were detected with immunohistochemistry and confirmed that endometriotic lesions had significantly higher prevalence of new vessels (CD31 only positive) than the uterus and control tissues. The diagnostic value of gadofosveset-trisodium to detect endometriosis should be tested in human settings.

PLoS One. 2012;7(3):e33941. Epub 2012 Mar 19.

Women with endometriosis are more likely to suffer from migraines: a population-based study.

Yang MH, Wang PH, Wang SJ, Sun WZ, Oyang YJ, Fuh JL.


Department of Computer Science and Information Engineering, National Taiwan University, Taipei City, Taiwan, Republic of China.


Previous research suggests that a co-morbid relationship exists between migraine and endometriosis; however, results have been inconsistent. In addition, female hormones, which are important in the pathogenesis and management of endometriosis, have been reported to precipitate migraine attacks and may confound the results. The aim of this population-based cohort study was to explore the relationship between migraine and endometriosis in women of reproductive age (18-51 years). Data were derived from the National Health Insurance Research Database of Taiwan, which contains outpatient and inpatient records from 2000 to 2007. Our study cohort included 20,220 endometriosis patients and 263,767 controls without endometriosis. We analyzed the prevalence of migraine in these women as recorded during the eight years of the database. Our results found that patients with endometriosis were more likely to suffer migraine headaches compared to controls (odds ratio [OR], 1.70; 95% confidence interval [CI] [1.59, 1.82]; p<0.001). In addition, the co-morbid association between migraine and endometriosis remained significant after the data were controlled for age and frequently utilized hormone therapies (OR, 1.37; 95% CI, [1.27, 1.47]; p<0.001). The results of this cohort study support the existence of a co-morbid relationship between migraine and endometriosis, even after adjusting for the possible effects of female hormone therapies on migraine attacks.

PLoS One. 2012;7(2):e31758. Epub 2012 Feb 21.

Sprouted innervation into uterine transplants contributes to the development of hyperalgesia in a rat model of endometriosis.

McAllister SL, Dmitrieva N, Berkley KJ.


Program in Neuroscience, Florida State University, Tallahassee, Florida, United States of America.


Endometriosis is an enigmatic painful disorder whose pain symptoms remain difficult to alleviate in large part because the disorder is defined by extrauteral endometrial growths whose contribution to pain is poorly understood. A rat model (ENDO) involves autotransplanting on abdominal arteries uterine segments that grow into vascularized cysts that become innervated with sensory and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used behavioral, physiological, and immunohistochemical methods to test the hypothesis that cyst innervation contributes to the development of this hyperalgesia after transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts at two weeks, sprouted further and more densely into the cyst wall by four weeks, and matured by six weeks post-transplant. Sensory fibers became abnormally functionally active between two and three weeks post-transplant, remaining active thereafter. Vaginal hyperalgesia became significant between four and five weeks post-transplant, and stabilized after six to eight weeks. Removing cysts before they acquired functional innervation prevented vaginal hyperalgesia from developing, whereas sham cyst removal did not. Thus, abnormally-active innervation of ectopic growths occurs before hyperalgesia develops, supporting the hypothesis. These findings suggest that painful endometriosis can be classified as a mixed inflammatory/neuropathic pain condition, which opens new avenues for pain relief. The findings also have implications beyond endometriosis by suggesting that functionality of any transplanted tissue can be influenced by the innervation it acquires.

PLoS One. 2012;7(1):e29252. Epub 2012 Jan 5.

Hydroxybenzothiazoles as new nonsteroidal inhibitors of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1).

Spadaro A, Negri M, Marchais-Oberwinkler S, Bey E, Frotscher M.


Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrücken, Germany.


17β-estradiol (E2), the most potent estrogen in humans, known to be involved in the development and progession of estrogen-dependent diseases (EDD) like breast cancer and endometriosis. 17β-HSD1, which catalyses the reduction of the weak estrogen estrone (E1) to E2, is often overexpressed in breast cancer and endometriotic tissues. An inhibition of 17β-HSD1 could selectively reduce the local E2-level thus allowing for a novel, targeted approach in the treatment of EDD. Continuing our search for new nonsteroidal 17β-HSD1 inhibitors, a novel pharmacophore model was derived from crystallographic data and used for the virtual screening of a small library of compounds. Subsequent experimental verification of the virtual hits led to the identification of the moderately active compound 5. Rigidification and further structure modifications resulted in the discovery of a novel class of 17β-HSD1 inhibitors bearing a benzothiazole-scaffold linked to a phenyl ring via keto- or amide-bridge. Their putative binding modes were investigated by correlating their biological data with features of the pharmacophore model. The most active keto-derivative 6 shows IC₅₀-values in the nanomolar range for the transformation of E1 to E2 by 17β-HSD1, reasonable selectivity against 17β-HSD2 but pronounced affinity to the estrogen receptors (ERs). On the other hand, the best amide-derivative 21 shows only medium 17β-HSD1 inhibitory activity at the target enzyme as well as fair selectivity against 17β-HSD2 and ERs. The compounds 6 and 21 can be regarded as first benzothiazole-type 17β-HSD1 inhibitors for the development of potential therapeutics.

Reprod Sci. 2012 Jan;19(1):64-9. Epub 2011 Nov 3.

Reduced levels of serum pigment epithelium-derived factor in women with endometriosis.

Chen L, Fan R, Huang X, Xu H, Zhang X.


Women’s Hospital, Zhejiang University School of Medicine, Hangzhou Zhejiang, P. R. China.


The authors previously demonstrated decreased levels of pigment epithelium-derived factor (PEDF) in peritoneal fluid of women with endometriosis compared to women without endometriosis. Here, the authors determine whether women with endometriosis have altered levels of PEDF in serum. Peripheral blood samples were collected from 71 women with and without endometriosis (n = 43 and 28, respectively) before laparoscopic surgery. Concentrations of serum PEDF were measured by enzyme-linked immunosorbent assay. We detected lower levels of serum PEDF in women with endometriosis (16.3 ± 6.6 ng/mL) than in those without endometriosis (24.5 ± 7.3 ng/mL; P < .001). In women with endometriosis, the concentrations of serum PEDF were significantly lower in women with pain (n = 11, 12.6 ± 7.1 ng/mL) compared to women without pain (n = 32, 17.5 ± 6.0 ng/mL; P < .05). However, the concentrations of serum PEDF did not correlate with disease stage or site or infertility. In addition, the concentrations of serum PEDF did not show any difference in the phase of the cycle in either group. Our results suggest that reduced levels of serum PEDF in women with endometriosis and disease-related pain may play a role in the pathogenesis of this disease.

Rev Assoc Med Bras. 2012 Jan-Feb;58(1):26-32.

Evaluation of CA-125 and soluble CD-23 in patients with pelvic endometriosis: a case-control study.

Ramos IM, Podgaec S, Abrão MS, de Oliveira R, Baracat EC.


Endometriosis Division, Obstetrics and Gynecology Department, Universidade de São Paulo, São Paulo, SP, Brazil.



To evaluate serum concentrations of CA-125 and soluble CD-23 and to correlate them with clinical symptoms, localization and stage of pelvic endometriosis and histological classification of the disease.


Blood samples were collected from 44 women with endometriosis and 58 without endometriosis, during the first three days (1st sample) and during the 7th, 8th and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain evaluations (visual analog scale) and biomarkers concentrations.


Serum levels of CA125 were higher in endometriosis patients when compared to the control group during both periods of the menstrual cycle evaluated in the study. This marker was also elevated in women with chronic pelvic pain, deep dyspareunia (2nd sample), dysmenorrhea (both samples) and painful defecation during the menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages of the disease in both samples and also in women with ovarian endometrioma. Concerning CD-23, no statistically significant differences were observed between groups.


The concentrations of CA-125 were higher in patients with endometriosis than in patients without the disease. No significantly differences were observed for soluble CD-23 levels between groups.

Rev Bras Ginecol Obstet. 2012 Jan;34(1):11-5.

Importance of quality of life assessment in patients with endometriosis.

[Article in Portuguese]

Minson FP, Abrão MS, Sardá Júnior J, Kraychete DC, Podgaec S, Assis FD.


Programo de Dor do Hospital Israelita Albert Einstein, São Paulo, SP, Brasil.



The present study examined the relationship between some clinical variables and quality of life in a group of patients with endometriosis.


A total of 130 women seen at a multidisciplinary center specializing in gynecology endometriosis in 2008 participated in the study. This was a cross-sectional study conducted with a convenience sample. The diagnosis of endometriosis was performed by biopsy according to the criteria of the American Society for Reproductive Medicine. The clinical and demographic data were collected from the patients’ records. Pain intensity was assessed by a visual numerical scale (0-10), and data on the quality of life were collected using the SF-36. Data analysis consisted of descriptive and inferential statistical tests, Spearman correlation coefficient and Kruskal-Wallis test to compare scores between groups. Nonparametric tests were used for analysis because data were not normally distributed.


The patients were 21 to 54 years of age or 34, standard diversion (SD)=6.56], 87% had a university degree, and 75% were married. Seventeen percent reported cases of endometriosis in the family. The average time of onset of symptoms was 4.5 years (SD=6.6), 63% of patients were in stage 3 or 4 of endometriosis 36% of patients had severe or disabling dysmenorrhea and the average intensity of pain according to a visual numerical scale was of 5.6 (SD=3.5). Results suggest that the staging of the disease did not determine the intensity of pain. The time of onset of symptoms also showed no relationship to pain intensity and SF-36 scores. On the other hand, the intensity of pain was associated with lower scores on some scales of the SF-36.


Patients with endometriosis had lower scores of quality of life than the general population and lower than those of some other diseases.

Rofo. 2012 Jan;184(1):48-52. Epub 2011 Dec 9.

Change in health-related quality of life and change in clinical symptoms after uterine artery embolization in patients with symptomatic adenomyosis uteri – evaluation using a standardized questionnaire.

[Article in German]

Froeling V, Scheurig-Muenkler C, Steffen IG, Schreiter NF, Kröncke TJ.


Universitätsmedizin Charité Berlin, Radiologie, Berlin. vera.froeling@charite.de



To evaluate the clinical response of uterine artery embolization (UAE) in women with symptomatic uterine adenomyosis by comparing health-related quality of life and symptom severity before and after UAE using a standardized questionnaire.


This longitudinal study at two time points included 17 patients with a median age of 47.1 years with symptomatic uterine adenomyosis (n = 7 pure adenomyosis; n = 10 with concomitant fibroids). The diagnosis was based on clinical symptoms and magnetic resonance imaging (MRI) criteria. Data on health-related quality of life and severity of symptoms before and after UAE were obtained by the standardized “Uterine Fibroid Symptom and Quality of Life” (UFS-QOL) questionnaire and correlated in the following. Treatment failure was defined as the need for a second invasive procedure because of recurrent symptoms or persistent symptoms after UAE.


The median interval between the evaluation of the UFS-QOL questionnaire before and after UAE was 46.0 months. 70.6 % (12/17; 95 % confidence interval 44.0 %  - 88.6 %) of the patients had therapy response with a significant improvement of health-related quality of life and clinical symptoms (p-value = 0.002). The therapy failure rate was 29.4 % (5/17; 95 % confidence interval 11.4 %  – 56.0 %). One patient underwent dilatation and curettage and four patients underwent hysterectomy because of therapy failure.


UAE to treat symptomatic adenomyosis uteri can significantly improve the health-related quality of life and clinical symptoms. However, therapy failure is possible in up to one-third of patients.

Rom J Morphol Embryol. 2012;53(2):433-7.

Ureteral stenosis due to endometriosis.

Traşcă ET, Traşcă E, Tiţu A, Riza ML, Busuioc I.


Department of Surgery, University of Medicine and Pharmacy of Craiova, Romania; etrasca@yahoo.com.


Endometriosis is characterized by the presence of endometrial tissue outside the uterine cavity, with potential to undergo malignant transformation. We report the case of a 36-year-old patient with a clinical and imagistic diagnosis of left vaginal pouch and left parametrium tumor. The patient presented lumbar and pelvic pain, dysuria and polakyuria. Ultrasound revealed changes in the left kidney confirmed by the CT scan, which also revealed the presence of a tumor in the left parametrium infiltrating the bladder, juxtavesical ureter, uterus and cervix. Laboratory tests were within normal limits. Surgery consisted of interadnexal hysterectomy, proximal colpectomy, left distal ureterectomy with ureterocystoneostomy. Pathological examination established the final diagnosis of infiltrative deep endometriosis involving the urinary tract. In the case of a young fertile patient with gynecological symptoms and morphofunctional changes of the urinary system, urinary tract endometriosis should always be a diagnostic option.

Semin Reprod Med. 2012 Jan;30(1):39-45. Epub 2012 Jan 23.

Role of estrogen receptor-β in endometriosis.

Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, Tokunaga H, Su EJ.


Division of Reproductive Biology Research, Department Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. s-bulun@northwestern.edu


Endometriosis is an estrogen-dependent disease. The biologically active estrogen, estradiol, aggravates the pathological processes (e.g., inflammation and growth) and the symptoms (e.g., pain) associated with endometriosis. Abundant quantities of estradiol are available for endometriotic tissue via several mechanisms including local aromatase expression. The question remains, then, what mediates estradiol action. Because estrogen receptor (ER)β levels in endometriosis are >100 times higher than those in endometrial tissue, this review focuses on this nuclear receptor. Deficient methylation of the ERβ promoter results in pathological overexpression of ERβ in endometriotic stromal cells. High levels of ERβ suppress ERα expression. A severely high ERβ-to-ERα ratio in endometriotic stromal cells is associated with suppressed progesterone receptor and increased cyclo-oxygenase-2 levels contributing to progesterone resistance and inflammation. ERβ-selective estradiol antagonists may serve as novel therapeutics of endometriosis in the future.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Semin Reprod Med. 2012 Jan;30(1):3-4. Epub 2012 Jan 23.

The important role of estrogen receptor-β in women’s health.

Su EJ.

Steroids. 2012 Jan;77(1-2):27-35. Epub 2011 Nov 13.

Tissue physiology and pathology of aromatase.

Stocco C.


Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, United States. costocco@uic.edu


Aromatase is expressed in multiple tissues, indicating a crucial role for locally produced oestrogens in the differentiation, regulation and normal function of several organs and processes. This review is an overview of the role of aromatase in different tissues under normal physiological conditions and its contribution to the development of some oestrogen-related pathologies.

Tohoku J Exp Med. 2012;226(2):95-9.

Primate model research for endometriosis.

Yamanaka A, Kimura F, Takebayashi A, Kita N, Takahashi K, Murakami T.


Department of Obstetrics and Gynecology, Shiga University of Medical Science, Otsu, Japan. ykiyoshi@belle.shiga-med.ac.jp


Endometriosis is defined as the existence of endometrial tissue outside the uterine cavity, and it includes a chronic, inflammatory reaction associated with female infertility and pelvic pain. Endometriosis occurs in 7 to 10% of women. Although it has been studied for more than 50 years, the pathogenesis and development of endometriosis are still poorly understood. There is no curative therapy for endometriosis, which often recurs after surgical or medical treatment. There is a consensus that the adverse current of menstrual blood plays a crucial role in the development of endometriosis. This places a major limitation on research using rodent models of endometriosis, although these are still widely employed, because rodents do not menstruate and endometriosis does not occur spontaneously in these animals. In fact, menstruation and spontaneous endometriosis only occur in women and some non-human primates, making models that employ non-human primates the best animal models for research into the pathogenesis, pathophysiology, spontaneous onset, and treatment of endometriosis. This review assesses the effectiveness and potential of the non-human primate models of endometriosis. It also describes the current findings and theories on the pathogenesis of endometriosis that have been obtained by research using non-human primates.

Ultrasound Obstet Gynecol. 2012 Jan;39(1):106-9. doi: 10.1002/uog.9062. Epub 2011 Dec 5.

Endometrial cancer and ultrasound: why measuring endometrial thickness is sometimes not enough.

Naftalin J, Nunes N, Hoo W, Arora R, Jurkovic D.


University College Hospital, London, UK.


Endometrial cancer is the commonest cancer of the female genital tract in the developed world. Ultrasound measurement of endometrial thickness is commonly used to triage patients with postmenopausal bleeding for histological sampling. The sensitivity of ultrasound in diagnosing endometrial cancer is high, but it has a small, well-defined false-negative rate. In this report we describe two cases, with histological confirmation, of postmenopausal women without any vaginal bleeding, who were subsequently diagnosed with advanced endometrial cancer. They were found to have a thin, normal endometrium on ultrasound. In both cases, histological examination was suggestive of endometrial cancer originating from foci of adenomyosis. These findings suggest that a proportion of the false-negative diagnoses of endometrial cancer on ultrasound could be caused by the disease being confined to the myometrium rather than as a result of suboptimal performance of ultrasound examination.

Urol Ann. 2012 Jan;4(1):6-12.

Urinary tract endometriosis: Review of 19 cases.

Kumar S, Tiwari P, Sharma P, Goel A, Singh JP, Vijay MK, Gupta S, Bera MK, Kundu AK.


Department of Urology, IPGME and R, SSKM Hospital, Kolkata, India.



The aim of our study was to evaluate the treatment outcomes of medical and surgical management of urinary tract endometriosis.


Urinary tract endometriosis patients enrolled between Jan 2006 and May 2010 were retrospectively reviewed. Preoperative datas (mode of presentation, diagnosis, imaging), intraoperative findings (location and size of lesion), postoperative histopathology and follow-up were recorded and results were analyzed and the success rate of different modalities of treatment was calculated.


In our study, of nineteen patients, nine had vesical involvement and ten had ureteric involvement. Among the vesical group, the success rate of transurethral resection followed by injection leuproide was 60% (3/5), while among the partial cystectomy group, the success rate was 100%. Among patients with ureteric involvement, success rate of distal ureterectomy and reimplantation was 100%, laparoscopic ureterolysis with Double J stenting followed by injection leuprolide was 75% while that of Gonadotropin- releasing hormone (GnRh) analogue alone was 67%.


One should have a high index of suspicion with irritative voiding symptoms with or without hematuria, with negative urine culture, in all premenopausal women to diagnose urinary tract endometriosis. Partial cystectomy is a better alternative to transurethral resection followed by GnRh analogue in vesical endometriosis. Approach to the ureter must be individualised depending upon the severity of disease and dilatation of the upper tract to maximise the preservation of renal function.

Virchows Arch. 2012 Jan;460(1):77-87. Epub 2011 Nov 26.

PIK3CA mutations and loss of ARID1A protein expression are early events in the development of cystic ovarian clear cell adenocarcinoma.

Yamamoto S, Tsuda H, Takano M, Tamai S, Matsubara O.


Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, Japan. dr21001@ndmc.ac.jp


Somatic mutations of PIK3CA and ARID1A are the most common genetic alterations observed in ovarian clear cell adenocarcinomas (CCA). In a previous report, we showed that PIK3CA gene mutations and loss of ARID1A expression occur early during the development of CCA. In the present study, using direct genomic DNA sequencing for exons 9 and 20 of PIK3CA and immunohistochemistry for ARID1A protein expression, we analyzed the association of these molecular alterations with various clinicopathological parameters in a total of 90 cases of primary ovarian CCA, including 42 previously examined cases. The presence of PIK3CA mutations, identified in 34 (39%) of the 88 informative cases, was significantly associated with a grossly cystic tumor, the presence of adjacent endometriosis, prominent papillary architecture of tumor growth, the presence of hyalinized and mucoid stroma, and the absence of clear cell adenofibroma components (P < 0.05, each). There was no significant association of PIK3CA mutations with other clinical variables, such as age, clinical stage, or clinical outcome of the patients. The intensity of immunoreactivity for ARID1A was assigned as negative, weakly positive, and strongly positive in 44%, 22%, and 33% of tumors, respectively. Compared to tumors immunoreactive for ARID1A, ARID1A-negative tumors were significantly associated with the presence of adjacent endometriosis (P = 0.025), but there was no statistically supported association with other examined clinicopathological parameters. Compared with CCAs strongly positive for ARID1A, CCAs negative for ARID1A more frequently harbor PIK3CA mutations (P = 0.013). PIK3CA gene mutations and ARID1A immunohistochemistry lacked prognostic significance. These data further support the idea that these molecular alterations occur as very early events during tumor development of ovarian CCA.

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