Am J Pathol. 2011 Dec 30. [Epub ahead of print]

Host-Derived TGFB1 Deficiency Suppresses Lesion Development in a Mouse Model of Endometriosis.

Hull ML, Zahied Johan M, Hodge WL, Robertson SA, Ingman WV.

Source

The Robinson Institute, Research Centre for Reproductive Health, and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia; Department of Obstetrics and Gynaecology, Women’s and Children’s Hospital, North Adelaide, Australia.

Abstract

Transforming growth factor-Beta 1 (TGFB1) is a multifunctional cytokine that is abundant in both endometriotic lesions and the peritoneal fluid in women with endometriosis. However, the role of TGFB1 in the development of endometriosis is as yet undefined. In the present study, we investigated the physiologic function of TGFB1 in endometriotic lesion development, using Tgfb1-null mutant mice on a background of severe combined immunodeficiency. Xenotransplantation of human eutopic endometrial tissue resulted in development of endometriosis-like lesions in 63% of ovariectomized estrogen-supplemented Tgfb1-null mutant mice and in 68% of wild-type control mice. Median lesion weight was reduced by 11-fold in Tgfb1-null mice compared with wild-type control mice, and the fraction of glandular epithelium in lesions from Tgfb1-null mice was reduced by 32% compared with that in control mice. In lesions from Tgfb1-null mice, the relative abundance of both macrophages and α-smooth muscle actin-positive myofibroblasts was reduced by 66% and 47%, respectively. Deficiency of TGFB1 neither altered the percentage of proliferating cells in the epithelial or stromal compartments of the lesions nor affected blood vessel density or vessel size. Observation of this study indicates that host-derived TGFB1 deficiency suppresses endometriotic lesion development and provides proof of principle that targeting TGFB1 signaling pathways in cells that support the survival of ectopic endometrium may be an effective therapeutic approach in women with endometriosis.

Clin Chem. 2011 Dec 28. [Epub ahead of print]

Circulating Epithelial Cells in Patients with Benign Colon Diseases.

Pantel K, Denève E, Nocca D, Coffy A, Vendrell JP, Maudelonde T, Riethdorf S, Alix-Panabières C.

Source

Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;

Abstract

BACKGROUND:

Detection of circulating tumor cells (CTCs) in the peripheral blood is a rapidly developing research field with clear clinical implications for the staging and monitoring of cancer patients. Current CTC assays, including the US Food and Drug Administration-cleared CellSearch® system, typically use markers [e.g., cytokeratins (CKs), the transmembrane protein EpCAM (epithelial cell adhesion molecule)] that are expressed on normal and malignant epithelial cells but not on the surrounding normal leukocytes.

METHODS:

We enrolled 53 patients with benign colon diseases (e.g., diverticulosis, benign polyps, Crohn disease, ulcerative rectocolitis, colonic endometriosis) and analyzed their peripheral blood with 2 previously validated CTC assays: the epithelial immunospot (EPISPOT) assay and the CellSearch system. The EPISPOT assay detects only viable, CK19-releasing CTCs that were enriched by depletion of CD45(+) leukocytes, whereas the CellSearch system detects CK-positive CTCs after positive EpCAM-based immunomagnetic enrichment.

RESULTS:

In patients with benign colon diseases, positive events that met the criteria for “tumor cells” were detected with both the CellSearch system (11.3%) and the CK19-EPISPOT assay (18.9%), whereas no positive events were detected in samples from healthy volunteers. Positive events were detected most frequently in patients with diverticulosis and Crohn disease. All positive events lacked expression of CD45, a common leukocyte antigen.

CONCLUSIONS:

These results indicate that patients with benign inflammatory colon diseases in particular can harbor viable circulating epithelial cells that are detectable with current CTC assays. This finding points to the need for further molecular characterization of circulating epithelial cells and has important implications for the use of CTC testing.

J Zoo Wildl Med. 2011 Dec;42(4):747-50.

Bilateral hydronephrosis secondary to endometriosis managed by endoscopic ureteral stent placement in a captive Guinea baboon (Papio papio).

Dallwig RK, Langan JN, Hatch DA, Terio KA, Demitros C.

Source

Chicago Zoological and Aquatic Animal Residency Program, University of Illinois, College of Veterinary Medicine, Urbana, Illinois 61802, USA. rdallwig@gmail.com

Abstract

Spontaneous endometriosis is an estrogen-dependent, progressive and painful disease that affects a variety of nonhuman primates, including several species of baboons (Papio sp.). This case documents multimodal management of severe endometriosis in a captive female baboon within a zoological institution. An 18-yr-old, intact female Guinea baboon (Papio papio) was found to have an enlarged uterus. Fifteen months post ovariohysterctomy, scarring associated with endometrial tissue resulted in ureteral strictures, bilateral hydronephrosis, and azotemia. Cystoscopic placement of bilateral ureteral stents with fluoroscopy was performed and resulted in short-term clinical improvement. The animal’s condition declined and euthanasia was elected 4 mo after ureteral stent placement. Severe endometriosis with secondary inflammation resulting in bilateral hydroureter and hydronephrosis, as well as concurrent cystitis, ureteritis, and pyelonephritis were confirmed at necropsy. Despite possible complications, ureteral stents can be considered a useful therapeutic option in patients with ureteral disease.

Obstet Gynecol Int. 2011;2011:719059. Epub 2011 Dec 13.

Endometriosis gene expression heterogeneity and biosignature: a phylogenetic analysis.

Abu-Asab M, Zhang M, Amini D, Abu-Asab N, Amri H.

Source

Laboratory of Immunology, Section of Immunopathology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Abstract

Endometriosis is a multifactorial disease with poorly understood etiology, and reflecting an evolutionary nature where genetic alterations accumulate throughout pathogenesis. Our objective was to characterize the heterogeneous pathological process using parsimony phylogenetics. Gene expression microarray data of ovarian endometriosis obtained from NCBI database were polarized and coded into derived (abnormal) and ancestral (normal) states. Such alterations are referred to as synapomorphies in a phylogenetic sense (or biomarkers). Subsequent gene linkage was modeled by Genomatix BiblioSphere Pathway software. A list of clonally shared derived (abnormal) expressions revealed the pattern of heterogeneity among specimens. In addition, it has identified disruptions within the major regulatory pathways including those involved in cell proliferation, steroidogenesis, angiogenesis, cytoskeletal organization and integrity, and tumorigenesis, as well as cell adhesion and migration. Furthermore, the analysis supported the potential central involvement of ESR2 in the initiation of endometriosis. The pathogenesis mapping showed that eutopic and ectopic lesions have different molecular biosignatures.

Front Biosci (Schol Ed). 2012 Jan 1;4:1151-71.

Endometrial biology during trophoblast invasion.

Modi DN, Godbole G, Suman P, Gupta SK.

Source

National Institute for Research in Reproductive Health, Jehangir Merwanji Street, Parel, Mumbai-400 012, India.

Abstract

Attainment of successful implantation depends upon the synchronized changes in the endometrium before and after the arrival of blastocyst into the uterine cavity. The cues obtained from the receptive endometrium helps in proliferation and differentiation of the trophoblast cells. During the course of invasive differentiation, the trophoblast cells undergo several morphological, biochemical and molecular changes to gain the invasive capabilities. In turn, close apposition of the developing embryo brings out functional and morphological changes into the hormone primed receptive endometrium. Global gene expression profiling of the endometrium in response to the developing embryo or in response to the pregnancy hormone, human chorionic gonadotropin, in primate and human models, suggest that the endometrial-embryo cross-talk mainly influences three biological processes. Biological processes getting influenced by the blastocyst “signals” are associated with immunomodulation, biosensing and invasion. Pro- and anti-invasive paracrine factors expressed by different endometrial cell populations regulate the trophoblast invasion through activation of diverse signaling pathways. Identification of the gene signatures involved in embryo-endometrial dialogue would enhance our understanding about the pathologies like miscarriages and endometriosis.

Front Biosci (Elite Ed). 2012 Jan 1;4:1724-30.

Endocrine disruptors in utero cause ovarian damages linked to endometriosis.

Signorile PG, Spugnini EP, Citro G, Viceconte R, Vincenzi B, Baldi F, Baldi A.

Source

Fondazione Italiana Endometriosi, Rome, Italy.

Abstract

Timed pregnant Balb-C mice were treated from day 1 of gestation to 7 days after delivery with the endocrine disruptor bisphenol a (BPA) (100, or 1,000 microg/kg/day). After delivery, pups were hold for three months; then, ovaries were analyzed in their entirety. We found that in the ovaries of BPA-treated animals the number of primordial follicles and of developing follicles was significantly lower than in the untreated animals. Moreover, the number of atretic follicles was significantly higher in the treated animals. Finally, we found that the animals displaying endometriosis-like phenotype had a more severe impairment of the ovaries in term of number of primordial and developing follicles in comparison with the other mice exposed to BPA. In conclusion, we describe for the first time a complex phenotype in mice, elicited by pre-natal exposition to BPA, that includes ovarian lesions and endometriosis. Considering the high incidence of endometriosis and of the premature ovarian failure associated to infertility in these patients, the data showed prompt a thoroughly reconsideration of the pathological framing of these lesions.

Front Biosci (Elite Ed). 2012 Jan 1;4:1654-62.

Fertility preservation in women with ovarian endometriosis.

Donnez J, Squifflet J, Jadoul P, Lousse JC, Dolmans MM, Donnez O.

Source

Universite Catholique de Louvain, Cliniques Universitaires St. Luc, Department of Gynecology, Institut de Recherche Experimentale et Clinique, Avenue Hippocrate 10, B-1200 Brussels, Belgium.

Abstract

Endometriosis is one of the most frequently encountered benign diseases in gynecology. Complete resolution of endometriosis is not yet possible, but therapy has essentially three main objectives: (1) to preserve and improve fertility, (2) to reduce pain, and (3) to delay recurrence for as long as possible. The aim of this paper is to focus on fertility preservation in women with severe endometriosis. In moderate and severe endometriosis, a medico-surgical approach remains the gold standard, but more and more papers are reporting a low ovarian reserve after laparoscopic cystectomy for endometriomas. Indeed, very frequently, normal ovarian tissue is excised together with the endometrioma wall. Ovarian surgery in endometriosis patients should therefore be performed by experienced surgeons in order to both preserve and improve fertility. Preservation of ovarian tissue should be considered in all patients at serious risk of future fertility impairment, particularly before any treatment likely to result in ovarian endometriosis recurrence and/or premature ovarian failure.

Front Biosci (Elite Ed). 2012 Jan 1;4:755-67.

Proteinase-activated receptors in the endometrium and endometriosis.

Osuga Y, Hirota Y, Yoshino O, Hirata T, Koga K, Taketani Y.

Source

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Abstract

Proteinase-activated receptors (PARs) are G protein-coupled receptors activated by various proteinases. PARs play important roles in haemostasis, thrombosis, and inflammation. PAR1 and PAR2 are expressed in endometrial cells from the eutopic endometrium and endometriotic cells derived from endometriotic lesions. A typical activator of PAR1, thrombin, and a typical activator of PAR2, tryptase, are produced in the endometrium as well as endometriotic lesions. PAR1 activation in endometrial stromal cells induces production of vascular endothelial growth factor and matrix metalloproteinases, and increases activities of tissue-type and urokinase-type plasminogen activator. PAR2 activation in endometrial stromal cells stimulates interleukin (IL)-8 and stem cell factor production and proliferation of the cells. PAR1 activation in endometriotic stromal cells induces production of IL-8, monocyte chemotactic protein-1, and cyclooxygenase-2, and proliferation of the cells. PAR2 activation in endometriotic stromal cells increases secretion of IL-6 and IL-8, and the number of the cells. These findings indicate a wide range of function of PAR1 and PAR2 in the endometrium and endometriosis, and suggest PAR1 and PAR2 as possible therapeutic targets for endometriosis.

Front Biosci (Elite Ed). 2012 Jan 1;4:23-40.

Peritoneal endometriosis is an inflammatory disease.

Lousse JC, Langendonckt AV, Defrere S, Ramos RG, Colette S, Donnez J.

Source

Universite Catholique de Louvain, Institut de Recherche Experimentale et Clinique (IREC), Department of Gynecology, 1200 Brussels, Belgium.

Abstract

Peritoneal endometriosis is a chronic inflammatory disease characterized by increased numbers of peritoneal macrophages and their secreted products. Inflammation plays a major role in pain and infertility associated with endometriosis, but is also extensively involved in the molecular processes that lead to peritoneal lesion development. Peritoneal oxidative stress is currently thought to be a major constituent of the endometriosis-associated inflammatory response. Excessive production of reactive oxygen species, secondary to peritoneal influx of pro-oxidants such as heme and iron during retrograde menstruation, may induce cellular damage and increased proinflammatory gene expression through nuclear factor-kappa B activation. In particular, prostaglandin biosynthetic enzyme expression is regulated by this transcriptional factor, and increased peritoneal prostaglandin concentrations have been demonstrated in endometriosis. In the light of available data collected from patient biopsies, as well as in vitro and in vivo studies, the respective involvement and potential molecular interactions of iron, nuclear factor-kappa B and prostaglandins in the pathogenesis of endometriosis are explored and discussed. The key role of peritoneal macrophages is emphasized and potential therapeutic targets are examined.

Eur J Obstet Gynecol Reprod Biol. 2011 Dec 24. [Epub ahead of print]

Essure(®) hydrosalpinx occlusion prior to IVF-ET as an alternative to laparoscopic salpingectomy.

Mijatovic V, Dreyer K, Emanuel MH, Schats R, Hompes PG.

Source

VU University Medical Center, Department of Reproductive Medicine, Amsterdam, The Netherlands.

Abstract

OBJECTIVE:

To investigate the success rate of proximal tubal occlusion with Essure(®) devices in subfertile women with unilateral or bilateral hydrosalpinx and to observe the results of subsequent treatment with IVF-ET and/or frozen embryo transfer.

STUDY DESIGN:

Prospective, single-arm, clinical study in 20 women with unilateral or bilateral hydrosalpinges (all visible on transvaginal ultrasound) due to undergo IVF-ET and/or frozen embryo transfer. In all patients, laparoscopy was considered to be contraindicated due to extensive pelvic adhesions.

RESULT(S):

In all patients the Essure(®) devices were placed in an ambulant setting without any complications. Proximal tubal occlusion was confirmed by hysterosalpingography in 19 out of 20 patients (95%) and in 26 of 27 treated tubes (96%). After 45 embryo transfer procedures in 19 patients, 18 pregnancies with 12 live births, 6 miscarriages and 1 immature delivery (probably related to cervical insufficiency leading to chorioamnionitis and subsequent rupture of the membranes) were observed.

CONCLUSION(S):

Essure(®) devices are effective in inducing proximal tubal occlusion in subfertile patients with hydrosalpinges. After artificial reproductive treatments a cumulative live birth rate per patient of 63% and a cumulative live birth rate per transfer of 27% were achieved. The latter was related to the large proportion of patients with severe endometriosis.

Anticancer Res. 2011 Dec;31(12):4301-6.

Association of p53 and CDKN1A genotypes with endometriosis.

Ying TH, Tseng CJ, Tsai SJ, Hsieh SC, Lee HZ, Hsieh YH, Bau DT.

Source

Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan, R.O.C.

Abstract

BACKGROUND:

The tumor suppressor p53 protein plays a critical role in different cellular processes in response to DNA damage and it is responsible for transcriptional induction of the p21 (CDKN1A/WAF1/CIP1) gene. Both p53 and p21 are thought to play major roles in the development of human malignancy. Polymorphic variants of p53 at codon 72, and CDKN1A at codon 31, have been found to be associated with cancer susceptibility, but few studies have investigated their effect on endometriosis risk.

MATERIALS AND METHODS:

In this hospital-based case-control study, we investigated the association of p53 codon 72 and CDKN1A codon 31 polymorphisms with endometriosis susceptibility in a Taiwanese population. In total, 180 patients with endometriosis, and 330 age-matched controls in Central Taiwan were recruited and genotyped.

RESULTS:

We found a significant difference in the distribution of the p53 genotype, but not the CDKN1A genotype, between the endometriosis and control groups. Individuals with the C (Pro) allele at p53 codon 72 had a 1.6-fold increased odds ratio of endometriosis, and those with Arg/Pro and Pro/Pro genotypes for p53 codon 72 had a 1.84- and 2.74-fold (95% confidence interval=1.17-2.92 and 1.58-4.74) increased risk of endometriosis compared to those with Arg/Arg, respectively. The distribution of haplotype combinations of p53 codon 72 and CDKN1A codon 31 was statistically different in the endometriosis and control groups. The percentages of the three subgroups with p53 CC homozygote were all higher in the endometriosis group than in the control group.

CONCLUSION:

Our findings suggest that the C (Pro) allele of p53 codon 72 may be associated with the development of endometriosis, and could serve as a potential biomarker for early prediction of this disease.

Arch Gynecol Obstet. 2011 Dec 25. [Epub ahead of print]

Right endometrioma is related with more extensive obliteration of the Douglas pouch.

Ulukus M, Yeniel AO, Ergenoglu AM, Mermer T.

Source

Department of Obstetrics and Gynecology, Ege University Faculty of Medicine, Bornova, 35100, Izmir, Turkey.

Abstract

OBJECTIVE:

To investigate that endometrioma is an asymmetric disease with left lateral predisposition as compared to other benign ovarian cyst and also, whether endometrioma side is related with endometriosis severity.

METHODS:

Operative and histopathologic findings of 340 women who underwent cystectomy for treatment of endometriotic (n = 239) and nonendometriotic ovarian cysts (n = 101) by laparoscopy (n = 268) or laparotomy (n = 72) between January 2005 and August 2009 were evaluated retrospectively. We compared left and right sided distribution of endometriotic and nonendometriotic ovarian cysts, and we also investigated the extent of endometriotic foci, obliteration of pouch of Douglas and endometriosis stage according to the revised American Fertility Society classification of endometriosis to assess whether endometrioma side is related with the severity of endometriosis.

RESULTS:

Of 239 women with endometriosis, endometrioma was found in the left ovary (n = 109), right ovary (n = 58) and bilaterally (n = 72). Of 101 control group women functional and dermoid cysts were found in the left ovary (n = 48), right ovary (n = 43) and bilaterally (n = 10). Among women with unilateral ovarian endometrioma (n = 167) a left cyst (63.3%) was found more frequently than a right cyst (34.7%) (P < 0.0001). In women with a left ovarian endometrioma pouch of Douglas was open in 99 (90.8%) cases. However, it was partially obliterated in 3 (2.8%) and completely obliterated in 7 (6.4%) cases. On the other hand, in women with a right endometrioma it was open in 44 (75.9%) cases and partially obliterated in 2 (3.4%) and completely obliterated in 12 (20.7%) cases. In women with a right endometrioma, the possibility of the pouch of Douglas obliteration is significantly higher than the women with a left endometrioma (P = 0.006).

CONCLUSION:

Moreover, we also showed that in women with a right endometrioma, incidence of the pouch of Douglas obliteration is higher and the endometriosis tends to be more severe compared to women with a left endometrioma. Our most relevant observation is obliteration of Douglas pouch which was found to be more extensive in women with right ovarian endometrioma. Our results showing left lateral predisposition of endometriomas are in agreement with the previous reports and highlight the retrograde menstruation theory for the pathogenesis of this enigmatic disorder.

Fertil Steril. 2011 Dec 22. [Epub ahead of print]

Physiologic activation of nuclear factor kappa-B in the endometrium during the menstrual cycle is altered in endometriosis patients.

González-Ramos R, Rocco J, Rojas C, Sovino H, Poch A, Kohen P, Alvarado-Díaz C, Devoto L.

Source

Instituto de Investigaciones Materno Infantil, Departamento de Obstetricia y Ginecología, Hospital San Borja-Arriarán, Facultad de Medicina, Universidad de Chile, Santiago, Chile.

Abstract

OBJECTIVE:

To evaluate nuclear factor kappaB (NF-κB) activation and NF-κB-p65 subunit activation, immunolocalization, and expression in the endometrium of healthy women and endometriosis patients throughout the menstrual cycle.

DESIGN:

Prospective observational study.

SETTING:

Affiliated hospital and university research laboratory.

PATIENT(S):

Twenty-four healthy women and 24 endometriosis patients.

INTERVENTION(S):

Menstrual, proliferative, and secretory endometrial biopsies.

MAIN OUTCOME MEASURE(S):

Assessment of NF-κB and p65 activation by protein-DNA binding assays and p65 localization and expression by immunohistochemistry.

RESULT(S):

Total NF-κB-DNA binding was constitutive and variable in human endometrium accross the menstrual cycle. Healthy women (physiologic conditions) showed higher p65-DNA binding in proliferative than in menstrual and secretory endometrium. Conversely, in endometriosis patients, p65-DNA binding was higher in proliferative and secretory endometrium than in menstrual endometrium. Endometrial epithelial cells showed higher p65 expression level score than endometrial stromal cells.

CONCLUSION(S):

NF-κB activity is constitutive, physiologic, and variable in human endometrium. The physiologic cyclic p65 activation pattern was altered in endometriosis patients, showing no cyclic variation between the proliferative and secretory phase of the menstrual cycle. The absence of decreased p65 activity in secretory endometrium from endometriosis patients is concurrent with progesterone resistance and could participate in endometrial biologic alterations during the implantation window in endometriosis patients.

Am Surg. 2011 Nov;77(11):E246-7.

Spontaneous umbilical endometriosis: a rare but clinically important entity.

Richard F, Collins J, Britt LD.

Source

Department of Surgery, Eastern Virginia Medical School, Norfolk, Virginia 23507, USA. richarf@evms.edu

J Minim Invasive Gynecol. 2012 Jan;19(1):113-7.

Laparoscopic extramucosal partial bladder resection in a patient with symptomatic deep-infiltrating endometriosis of the bladder.

Prager M, Wilson T, Krüger K, Ebert AD.

Source

German Endometriosis Centre Berlin, Campus Humboldt, Am Nordgraben 2, Berlin, Germany.

Abstract

Endometriosis is a complex disease, affecting the urinary tract, mainly the bladder, in 1% to 2% of cases. Thus far, partial cystectomy has been the treatment of choice for long-term relief of symptoms. Here, we describe the case of a 26-year-old patient with deep-infiltrating bladder endometriosis who was completely cured by laparoscopic extramucosal bladder resection. Diagnostic standards and factors affecting the rate of success for this additional option in endometriosis surgery are discussed.

J Reprod Med. 2011 Nov-Dec;56(11-12):507-10.

Endometrioid adenocarcinoma arising from endometriosis: a case report.

Micha JP, Mendivil AA, Epstein HD, Laflamme LA, Goldstein BH.

Source

Gynecologic Oncology Associates, Newport Beach, CA 92663, USA.

Abstract

BACKGROUND:

Endometriosis is frequently identified in the ovaries, rectum, pelvic peritoneum, cervix and vagina. However, endometriosis undergoing malignant transformation is a rare event, particularly when the condition manifests itself promptly after initial surgical management.

CASE:

We present a case involving a 52-year-old woman who tested positive for the BRCA1 mutation and was diagnosed with endometriosis in 1999. Two years following treatment, the patient presented with an endometrioid adenocarcinoma; pathologic evaluation indicated that the neoplasm originated from the endometriosis.

CONCLUSION:

Malignant transformation is a very unusual event and reportedly occurs over several years. Nevertheless, considering the current patient’s relatively sudden onset of disease, oncologists should maintain a high index of suspicion in high-risk patients treated surgically for endometriosis who re-present with pelvic symptoms.

J Reprod Med. 2011 Nov-Dec;56(11-12):497-503.

Efficacy of the levonorgestrel-releasing intrauterine device in the treatment of recurrent pelvic pain in multitreated endometriosis.

Matorras R, Ballesteros A, Prieto B, Ocerin I, Expósito A, Pijoan JI, Crisol L.

Source

Human Reproduction Unit, Department of Obstetrics and Gynecology, Cruces Hospital, País Vasco University, Baracaldo, Vizcaya, Spain. roberto.matorras@osakidetza.net

Abstract

OBJECTIVE:

To assess the value of the levonorgestrel-releasing intrauterine device (LNG-IUD) in the treatment of pelvic pain in patients with endometriosis in which previous medical and surgical treatments have failed.

STUDY DESIGN:

This prospective study evaluated pelvic pain by means of both a visual analog grading scale and a verbal descriptive grading scale. Pain was evaluated before insertion of the LNG-IUD and afterwards, at 3-month intervals. Adverse effects and reasons for removal were recorded. Me dian follow-up was 22 months (range, 3-36 months). Response rates were expressed as a percentage of the initial cohort in whom the LNG-IUD was inserted, including cases in which the LNG-IUD was extracted.

RESULTS:

Three months after LNG-IUD insertion, almost 50% of patients reported an improvement in pain symptoms, with this figure rising to 60% after 6 months and almost 70% by the end of follow-up. A trend of better responses was observed when endometriosis was diagnosed <10 years before, as well as in stage I-II endometriosis, but these differences were not statistically significant.

CONCLUSION:

In endometriosis patients with recurrent pelvic pain in whom previous medical and surgical treatments have failed, LNG-IUD insertion should be considered before radical surgery is performed.

AJR Am J Roentgenol. 2012 Jan;198(1):98-105.

CT antegrade colonography to assess proctectomy and temporary diverting ileostomy complications before early ileostomy takedown in patients with low rectal endometriosis.

Gouya H, Oudjit A, Leconte M, Coste J, Vignaux O, Dousset B, Legmann P.

Source

Department of Radiology, University Paris Descartes Paris V, Cochin Hospital, Assistance Publique Hôpitaux de Paris, 27 rue du Faubourg Saint Jacques, 75014 Paris, Cedex 14, France. martinjeang@yahoo.fr

Abstract

OBJECTIVE:

The purpose of this study is to describe an imaging method based on a CT technique, CT antegrade colonography, for the evaluation of low anastomosis and to evaluate the value of CT antegrade colonography before early ileostomy closure after proctectomy in low rectal endometriosis.

MATERIALS AND METHODS:

One hundred ninety-five patients referred for low rectal endometriosis underwent proctectomy and were eligible for early ileostomy closure. All patients underwent standard antegrade fluoroscopy (n=77) or CT antegrade colonography (n=118) 8 days after surgery. The negative predictive values, positive predictive values, sensitivity, specificity, and likelihood ratio of standard antegrade fluoroscopy and CT antegrade colonography in detecting anastomotic leakage and abscesses were assessed. The reference standard for positive and negative examinations was based on clinical follow-up, imaging, surgical, or interventional procedure findings.

RESULTS:

Negative and positive predictive values for detecting anastomotic leakage were 100% (95% CI, 96.8-100%) and 100% (95% CI, 39.8-100%), respectively, for CT antegrade colonography and 98.6% (95% CI, 92.4-100%) and 100% (95% CI, 54.1-100%), respectively, for standard antegrade fluoroscopy. The negative and positive predictive values for detecting abscess were 100% (95% CI, 96.8-100%) and 100% (95% CI, 47.8-100%), respectively, for CT antegrade colonography and 97.3% (95% CI, 90.8-99.7%) and 100% (95% CI, 2.5-100%), respectively, for standard antegrade fluoroscopy.

CONCLUSION:

CT antegrade colonography may play a major role in the evaluation of low anastomosis protected by an ileostomy after proctectomy in low rectal endometriosis, leading to the development of a new strategy with early restoration of the intestinal continuity.

Fertil Steril. 2011 Dec 20. [Epub ahead of print]

Peroxisome proliferating activating receptor gamma-independent attenuation of interleukin 6 and interleukin 8 secretion from primary endometrial stromal cells by thiazolidinediones.

McKinnon B, Bersinger NA, Mueller MD.

Source

Department of Obstetrics and Gynecology, Inselspital, Berne University Hospital, University of Berne, Berne, Switzerland.

Abstract

OBJECTIVE:

To assess the effect of thiazolidinediones on the regulation of inflammatory cytokines related to endometriosis in endometrial tissue and determine whether these effects occur via activation of the peroxisome proliferating activating receptor gamma (PPAR)-γ.

DESIGN:

In vitro study using eutopic endometrial tissue.

SETTING:

University hospital.

PATIENT(S):

Premenopausal women undergoing laparoscopy for infertility or abdominal pain.

INTERVENTION(S):

Isolation of endometrial stromal cells and the culture of these cells in the presence of thiazolidinediones, ciglitazone and pioglitazone, both with and without a pretreatment of the specific, irreversible PPAR-γ antagonist GW9662.

MAIN OUTCOME MEASURE(S):

Quantitation of interleukin (IL)-6 and IL-8 released into the cell culture medium by ELISA. Real-time polymerase chain reaction to quantitate PPAR-γ gene expression in the primary cell preparations and the expression of IL-6 and IL-8 after thiazolidinedione treatment.

RESULT(S):

Treatment of stromal cells with thiazolidinediones attenuated IL-6 and IL-8 release in a dose-dependent manner. This effect was not inhibited by GW9662 pretreatment. Ciglitazone induced IL-6 messenger RNA expression, an effect that was suppressed by GW9662 pretreatment.

CONCLUSION(S):

Thiazolidinediones decrease the proinflammatory cytokines IL-6 and IL-8 in endometrial stromal cells via a PPAR-γ-independent mechanism. A better understanding of the anti-inflammatory action of this class of drugs may improve their safety and efficacy for endometriosis treatment.

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.

Source

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.

Abstract

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.

J Gastroenterol Hepatol. 2012 Jan;27(1):181. doi: 10.1111/j.1440-1746.2011.06956.x.

Education and imaging. Gastrointestinal: refractory ulcerative colitis complicated by colonic stricturing endometriosis.

Sim S, Johnston M, Crowley P, Froomes P.

Source

Department of Gastroenterology, Austin Hospital, Melbourne, Victoria, Australia.

Radiology. 2012 Feb;262(2):538-43. Epub 2011 Dec 20.

Levator Ani Muscle Complex: Anatomic Findings in Nulliparous Patients at Thin-Section MR Imaging with Double Opacification.

Loubeyre P, Copercini M, Petignat P, Dubuisson JB.

Source

Departments of Imaging and Obstetrics and Gynecology, Geneva University Hospitals, Rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland.

Abstract

Purpose: To determine levator ani muscle complex anatomic findings in nulliparous patients at magnetic resonance (MR) imaging examinations performed with opacification of the vagina and rectum with ultrasonographic gel. Materials and Methods: The institutional review board approved this retrospective study, and the informed consent requirement was waived. Findings from pelvic MR imaging examinations with double opacification in 123 consecutive nulliparous patients (mean age, 32.13 years; age range, 17-45 years) who were suspected of having endometriosis were reviewed. The pubococcygeal muscles were analyzed on coronal sections obtained through the middle part of the vagina, perineal body, and anal canal. The puborectalis muscles were analyzed on coronal sections obtained through the perineal body. The iliococcygeal muscles were analyzed on coronal sections obtained through the rectum. Miscellaneous findings such as visibility of deep transverse muscles of the perineum, perineal body, and focal muscle defects were also noted. Results: In 56% (69 of 123) of patients, at least one morphologic variant (thinning or aplasia) of a muscle of the levator ani complex was noted. Variants of puborectalis muscles were noted in 6% of patients. Variants of iliococcygeal muscles were noted in 13%. Variants of pubococcygeal muscles were noted in 32% at the anal canal level, in 49% at the perineal body level, and in 49% at the vaginal level. Variants of pubococcygeal muscles were noted on the left side in 53 patients (77% of pubococcygeal muscle variants). Conclusion: Numerous morphologic variants of the levator ani muscle complex are noted at coronal thin-section MR imaging with double opacification. Most involve the pubococcygeal muscle on the left side at perineal body and vaginal levels. Whether some of these anatomic findings may favor prolapse after vaginal birth may be questioned.

Pan Afr Med J. 2011;10:33. Epub 2011 Nov 8.

Exceptional cause of bowel obstruction: rectal endometriosis mimicking carcinoma of Rectum – a case report.

Sassi S, Bouassida M, Touinsi H, Mongi Mighri M, Baccari S, Chebbi F, Bouzeidi K, Sassi S.

Source

Department of surgery, Mohamed Thahar Maamouri Hospital, Nabeul, Tunisia.

Abstract

Endometriosis with intestinal serosal involvement is not uncommon in women of childbearing age. However, endometriosis presenting as colon obstruction is rare and occurs in less than 1% of cases. The Lack of pathognomonic signs makes the diagnosis difficult, mostly because the main differential diagnosis is with neoplasm, even during the intervention. Reported here is a case of a 35-year -old woman presenting with bowel obstruction due to rectal endometriosis. The patient presented signs and symptoms of bowel obstruction. Colonoscopy and radiological findings were suggestive of rectal carcinoma. Surgeons performed an anterior resection with right salpingectomy. Histopathology diagnosed bowel endometriosis. This case demonstrates the difficulty of establishing an accurate pre- and intra- operative diagnosis and the ability of intestinal endometriosis to mimic colon cancer.

Mol Hum Reprod. 2011 Dec 19. [Epub ahead of print]

Association of E-cadherin single nucleotide polymorphisms with the increased risk of Endometriosis in Indian women.

Govatati S, Tangudu NK, Deenadayal M, Chakravarty B, Shivaji S, Bhanoori M.

Source

Department of Biochemistry, Osmania University, Hyderabad – 500 007, INDIA.

Abstract

The objective of the present study was to investigate the association between gene E-cadherin single nucleotide polymorphisms (SNPs) and risk of developing endometriosis in Indian women and to evaluate the role of E-cadherin expression in the pathophysiology of endometriosis. A genetic association study was conducted in 715 endometriosis cases and 500 controls of Indian origin. We genotyped -160 C/A, +54 C/T and -347 G/GA SNPs of gene E-cadherin by PCR-sequencing and PCR-RFLP techniques. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D’) for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand genetic contributions to the pathophysiology of endometriosis, the expression pattern of E-cadherin in the endometrium of women with and without endometriosis was analyzed by Western blot and Immunohistochemical analysis. The frequencies of -347GA/GA (P = 0.026), -160A/A (P = 0.0019) genotypes and -347G/-160A/+54C (P = 0.007), -347GA/-160A/+54C (P < 0.0001) haplotypes were significantly different between patients and controls. Strong linkage disequilibrium was observed between -347G/GA and -160C/A loci (D’ = 0.64) when compared to -347G/GA and +54C/T (D’ = 0.585) or -160C/A and +54C/T (D’ = 0.05) loci in cases. Furthermore, increased membranous E-cadherin expression was observed in cases than in controls. The expression seems to be genotype dependent. In conclusion, the E-cadherin -347GA/GA, -160A/A genotypes and -347GA/-160A/+54C, -347G/-160A/+54C haplotypes may jointly modify the risk of endometriosis in Indian women. In addition, the differential expression of E-cadherin may play an important role in pathogenesis of endometriosis.

Gut. 2011 Dec 19. [Epub ahead of print]

Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study.

Jess T, Frisch M, Jørgensen KT, Pedersen BV, Nielsen NM.

Source

Statens Serum Institut, Copenhagen, Denmark.

Abstract

BackgroundAn association between endometriosis and certain autoimmune diseases has been suggested. However, the impact of endometriosis on risk of inflammatory bowel disease (IBD) remains unknown.ObjectiveTo assess the risk of Crohn’s disease (CD) and ulcerative colitis (UC) in an unselected nationwide Danish cohort of women with endometriosis.DesignBy use of national registers, 37 661 women hospitalised with endometriosis during 1977-2007 were identified. The relative risk of developing IBD after an endometriosis diagnosis was calculated as observed versus expected numbers and presented as standardised incidence ratios (SIRs) with 95% CIs.ResultsWomen with endometriosis had a increased risk of IBD overall (SIR=1.5; 95% CI 1.4 to 1.7) and of UC (SIR=1.5; 95% CI 1.3 to 1.7) and CD (SIR=1.6; 95% CI 1.3 to 2.0) separately, even 20 years after a diagnosis of endometriosis (UC: SIR=1.5; 95% CI 1.1 to 2.1; CD: SIR=1.8; 95% CI 1.1 to 3.2). Restricting analyses to women with surgically verified endometriosis suggested even stronger associations (UC: SIR=1.8; 95% CI 1.4 to 2.3; CD: SIR=1.7; 95% CI 1.2 to 2.5).ConclusionThe risk of IBD in women with endometriosis was increased even in the long term, hence suggesting a genuine association between the diseases, which may either reflect common immunological features or an impact of endometriosis treatment with oral contraceptives on risk of IBD.

Phytother Res. 2011 Dec 20. doi: 10.1002/ptr.3694. [Epub ahead of print]

Curcumin Attenuates TNF-α-induced Expression of Intercellular Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1 and Proinflammatory Cytokines in Human Endometriotic Stromal Cells.

Kim KH, Lee EN, Park JK, Lee JR, Kim JH, Choi HJ, Kim BS, Lee HW, Lee KS, Yoon S.

Source

Department of Obstetrics and Gynecology, Pusan National University School of Medicine, Busan, 602-739, Korea; Medical Research Institute, Pusan National University Hospital, Busan, 602-739, Korea.

Abstract

Curcumin, a naturally occurring polyphenolic compound from Curcuma longa, has long been used in folk medicine as an antiinflammatory remedy in Asian countries. Endometriosis is a chronic gynecological inflammatory disorder in which immune system deregulation may play a role in its initiation and progression. A number of mediators, including cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1); proinflammatory cytokines such as tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), IL-6 and IL-8; and chemokines such as monocyte chemotactic protein-1 (MCP-1), play key roles in the pathogenesis of endometriosis. The aim of our study was to explore the effect of curcumin on the expression of these critical molecules in human ectopic endometriotic stromal cells isolated from women with endometriosis. Endometriotic stromal cells treated with curcumin showed marked suppression of TNF-α-induced mRNA expression of ICAM-1 and VCAM-1. Curcumin treatment also significantly decreased the TNF-α-induced cell surface and total protein expression of ICAM-1 and VCAM-1 in a dose-dependent manner. In addition, treatment of endometriotic stromal cells with curcumin markedly inhibited TNF-α-induced secretion of IL-6, IL-8 and MCP-1. Furthermore, curcumin inhibited the activation of transcription factor NF-κB, a key regulator of inflammation, in human endometriotic stromal cells. These findings suggest that curcumin may have potential therapeutic uses in the prevention and treatment of endometriosis.

Acta Obstet Gynecol Scand. 2011 Dec 19. doi: 10.1111/j.1600-0412.2011.01346.x. [Epub ahead of print]

Randomized comparison of superovulation with letrozole vs. clomiphene citrate in an IUI program for women with recently surgically treated minimal to mild endometriosis.

Abu Hashim H, Rakhawy ME, Elaal IA.

Source

Department of Obstetrics & Gynecology Department of Diagnostic Radiology Department of Clinical Pathology, Mansoura Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Abstract

Objective. To evaluate pregnancy rates with letrozole and clomiphene citrate (CC) alone for superovulation in an intrauterine insemination program for women with recently surgically treated minimal to mild endometriosis. Design. A randomized controlled trial following the CONSORT criteria. Setting. University teaching hospital and a private practice setting. Patients. 136 women with primary infertility due to minimal to mild endometriosis who did not achieve pregnancy after six to 12 months following laparoscopic treatment. Interventions: Superovulation using 5mg letrozole/day (69 women, 220 cycles) or 100mg CC/day (67 women, 213 cycles) for five days combined with intrauterine insemination up to four cycles. Main outcome measures. Clinical pregnancy rate per cycle, cumulative pregnancy rate after four cycles, number of follicles, serum estradiol, endometrial thickness on the day of human chorionic gonadotropin administration, serum progesterone, miscarriage and live birth rates. Results. The clinical pregnancy rate per cycle and the cumulative pregnancy rate after four cycles were comparable (15.9 vs. 14.5% and 64.7 vs. 57.2%; p=0.82, p=0.71 in letrozole and CC groups, respectively). Two twin pregnancies occurred in the CC/intrauterine insemination group. Miscarriage and live birth rates were comparable (11.4 vs. 12.9% and 44.9 vs. 40.3%; p=0.47, p=0.62 in letrozole and CC groups, respectively). The total number of follicles and serum estradiol on the day of human chorionic gonadotropin administration were significantly increased in the CC group. Conclusions. Superovulation with letrozole is not more effective than clomiphene citrate alone in an intrauterine insemination program for women with minimal to mild endometriosis who did not achieve pregnancy after six to 12 months following laparoscopic treatment. ClinicalTrials.gov ID: NCT01334762.

Fertil Steril. 2012 Feb;97(2):367-372.e3. Epub 2011 Dec 15.

Deep infiltrating endometriosis is a determinant factor of cumulative pregnancy rate after intracytoplasmic sperm injection/in vitro fertilization cycles in patients with endometriomas.

Ballester M, Oppenheimer A, Mathieu d’Argent E, Touboul C, Antoine JM, Nisolle M, Daraï E.

Source

Department of Obstetrics and Gynecology, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France.

Abstract

OBJECTIVE:

To evaluate the cumulative pregnancy rate (CPR) per patient after in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles in patients with endometriomas and to evaluate the determinant factors of CPR per patient.

DESIGN:

Retrospective study from January 2007 to October 2008.

SETTING:

Tertiary care university hospital.

PATIENT(S):

103 patients who had undergone IVF treatment, comprising isolated endometriomas (n = 30) and endometriomas with associated deep infiltrating endometriosis (DIE) (n = 73).

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Clinical pregnancy rate after IVF-ICSI cycle.

RESULT(S):

The total number of cycles was 162, and the median number of cycles per patient was 1 (1 to 5). Fifty-eight women (56.3%) became pregnant. The total number of endometriomas and size of the largest endometrioma and bilateral endometriomas had no impact on the CPR per patient. Using multivariable analysis, the associated DIE and antimüllerian hormone serum level (≤1 ng/mL) were independent factors associated with a decrease in the pregnancy rate per patient. Overall, the CPR per patient was 73.7%, and it increased until the third cycle with no benefit for additional cycles. The CPR per patient for women with isolated endometriomas and women with endometriomas and associated DIE was 82.5% and 69.4%, respectively.

CONCLUSION(S):

Associated DIE has a negative impact on assisted reproduction results in patients with endometriomas. Moreover, our data show that after three IVF-ICSI cycles the CPR per patient is not improved and that surgery should be considered.

Ginecol Obstet Mex. 2011 Nov;79(11):697-710.

Diagnosis and treatment of endometriosis

[Article in Spanish]

Federación Mexicana de Colegios de Obstetricia y Ginecología.

 

J Laparoendosc Adv Surg Tech A. 2012 Jan;22(1):66-9. Epub 2011 Dec 13.

Laparoscopic rectal resection of deep infiltrating endometriosis.

Jelenc F, Ribič-Pucelj M, Juvan R, Kobal B, Sinkovec J, Salamun V.

Source

1 Department of Abdominal Surgery, University Medical Centre Ljubljana , Ljubljana, Slovenia .

Abstract

Abstract Purpose: Deep infiltrating endometriosis with colorectal involvement is a complex disorder, often requiring segmental bowel resection. Complete removal of all visible lesions is considered the adequate treatment of infiltrating endometriosis in order to reduce recurrence. In this article, we describe our experience with laparoscopic management of deep infiltrating endometriosis with involvement of the rectum. Methods: A retrospective analysis of data from patients with deep infiltrating endometriosis with rectal involvement who underwent a laparoscopic surgery in the years 2002-2009 at the Department of Obstetrics and Gynecology at our institution was done. Results: Between 2002 and 2009, a laparoscopic partial rectal resection was performed in 52 patients, and laparoscopic disk resection was performed in 4 cases with deep infiltrating endometriosis. The mean age of patients was 34.4 years (range, 22-62 years). Preoperative symptoms included dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility. The laparoscopic procedure was converted to formal laparotomy in 3 patients (5.4%). The mean duration of surgery was 145 minutes. Postoperative complications included 3 cases of anastomotic leakage with rectovaginal fistula in two cases and intraabdominal bleeding in 1 case. The mean hospital stay was 7 days. Postoperatively, nine patients had a normal delivery, two of them after in vitro fertilization treatment. Conclusion: Laparoscopic rectal resection for deep infiltrating endometriosis is a relatively safe procedure, when performed by a surgeon and a gynecologist with sufficient experience in laparoscopic colorectal surgery.

Arkh Patol. 2011 Jul-Aug;73(4):5-10.

Clinico-morphological features of endometrioid disease: adenomyosis, ovarian endometriosis, extragenital endometriosis

[Article in Russian]

Anichkov NM, Pechenikova VA, Kostiuchek DF.

Abstract

Adenomyosis, ovarian endometriosis and extragenital endometriosis are clinico-pathologic types of one nosologic form as endometrioid disease (ED). ED’s clinical presentations are various, but they are essentially characterized by a pain syndrome and disorder of menstrual cycle. The comparative clinico-pathologic analysis of adenomyosis, ovarian endometriosis, and extragenital endometriosis affords to suppose that theirs clinical course, the intensity and character of symptoms, as well as morphogenetic processes are generally determined by the organ localization. Topography of foci, theirs organ localization, morphological and morphofunctional features vary within one type of ED and even within one organ. So the separation of various ED’s morphofunctional forms, its clinico-phatological features and intensity of its morphofunctional activity is necessary. All forms of ED have general morphogenesis features including the various form of proliferation, secretion, regression, wave-like courses of dishormonal morphogenetic manifestation within one organ. Typical for all ED’s types pathologic synthesis of aromatase cytochrome P-450 promotes the local estrogens synthesis from androgens, transition of endometrioid heterotopias to the quite different level of existence and self-regulation contributing autonomous wave-like chronic ED’ clinic course.

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