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J Obstet Gynaecol Res. 2012 May 8. doi: 10.1111/j.1447-0756.2012.01860.x. [Epub ahead of print]

Selected cytokines and glycodelin A levels in serum and peritoneal fluid in girls with endometriosis.

Drosdzol-Cop A, Skrzypulec-Plinta V.

Source

Woman’s Health Institute and the Medical University of Silesia, Katowice, Poland.

Abstract

Aim:   The aim of this study was to determine the role of serum and peritoneal interleukin (IL)-6, tumor necrosis factor (TNF)-α and glycodelin A levels as diagnostic markers of endometriosis in adolescent girls. Material and Methods:  The study encompassed 50 adolescent girls, aged 13-19 years, after menarche and with chronic pelvic pain who qualified for diagnostic laparoscopy. The patients were allocated into two groups: group I (endometriosis group) consisted of subjects with diagnosed endometriosis (n = 33, 66%) and group II (control group) included those whose laparoscopic examinations revealed no evidence of endometriosis (n = 17, 34%). IL-6, TNF-α and glycodelin A concentrations in serum and peritoneal samples were assessed using commercially available human enzyme-linked immunosorbent assay kits. The value of P < 0.05 was adopted as the level of statistical significance. Results:  Compared with the control group, adolescent girls with endometriosis had significantly higher peritoneal fluid levels of: IL-6 (525.10 ± 1168.53 pg/mL vs 62.96 ± 82.35 pg/mL), TNF-α (5.79 ± 5.60 pg/mL vs 1.68 ± 1.24 pg/mL) and glycodelin A (94.24 ± 60.97 ng/mL vs 53.52 ± 41.43 ng/mL). Peritoneal IL-6, TNF-α and glycodelin A provided a good method of discrimination between subjects with endometriosis and controls. Using cut-off points for peritoneal fluid IL-6 (90.00 pg/mL), TNF-α (3.00 pg/mL) and glycodelin A (60.0 ng/mL), exceptionally high odds ratios (10.2; 14.6; 2.2) were obtained in the prediction of endometriosis in adolescents. Conclusions:  At the cut-off value of 3.00 pg/mL, peritoneal TNF-α can be a reliable screening marker for the prediction of endometriosis in adolescents, giving a 14.6-fold higher probability of endometriosis detection in girls with chronic pelvic pain.

Pain Pract. 2012 May 8. doi: 10.1111/j.1533-2500.2012.00559.x. [Epub ahead of print]

Management of Patients with Chronic Pelvic Pain Associated with Endometriosis Refractory to Conventional Treatment.

Martínez B, Canser E, Gredilla E, Alonso E, Gilsanz F.

Source

Pain Unit, Department of Obstetric Anesthesia, Madrid Autónoma University, Hospital Universitario La Paz, Madrid, Spain.

Abstract

  The literature contains numerous studies on the diagnosis, pathogenesis, atypical locations, and clinical (hormonal) and surgical management of the disorder. However, no information is available on the management of endometriosis involving pain refractory to the usual treatment from the perspective of a pain unit. Our hospital has a pain unit specifically dedicated to pain in gynecology and obstetrics. The unit has been functioning since December 2005, and 52% of the attended patients have CPP of different origins. Endometriosis is present in 48% of all patients with CPP and is the most prevalent pathology in our practice. It moreover poses an important challenge in view of its enormous complexity. A descriptive study was made of the management of 44 patients with endometriosis refractory to therapy, evaluated and treated over a period of 3 years in the Pain Unit of the Maternity Center of La Paz University Hospital (Madrid, Spain).

Reprod Sci. 2012 May 8. [Epub ahead of print]

Endometrial miR-200c is Altered During Transformation into Cancerous States and Targets the Expression of ZEBs, VEGFA, FLT1, IKKβ, KLF9, and FBLN5.

Panda H, Pelakh L, Chuang TD, Luo X, Bukulmez O, Chegini N.

Abstract

A number of microRNAs (miRNAs), including miR-200 family, are aberrantly expressed in endometriosis and endometrial cancer. Here we assessed the expression and functional aspects of miR-200c in endometrial tissues (N = 52) from normal endometrial biopsies (N = 15), endometrial tissues including those exposed to hormonal therapies (N = 20), and grade I-III endometrial cancer (N = 17). miR-200c expression was elevated in normal endometrial biopsies from mid- and late-luteal phase, and in endometrial tumors as compared to endometrial tissues from peri- and postmenopausal period (P < .05) and its pattern of temporal expression displayed an inverse relationship with the expression of ZEBs. The expression of E-cadherin (CDH1) varied, but expressed at low levels, specifically in endometrial tissues and endometrial tumors. The endometrial expression of ZEBs and CDH1 in patients who were exposed to Depo-Provera and gonadotropin-releasing hormone agonist GnRHa displayed a trend toward lower expression as compared to proliferative phase; however, treatment of Ishikawa cells with 17β-estradiol, progesterone, and medroxy progesterone acetate had modest effects on the expression of miR-200c and ZEBs without affecting CDH1 expression. Gain of function of miR-200c in Ishikawa cells repressed ZEBs, as well as VEGFA, FLT1, IKK, and KLF9 expression at transcriptional and translational levels through direct interaction with their respective 3’untranslated regions and increased the rate of their proliferation. These results indicated that endometrial miR-200c expression undergoes dynamic changes during transition from normal into cancerous states; possibly influenced by hormonal milieu and by targeting the expression of specific genes with key regulatory functions in cellular transformation, inflammation, and angiogenesis may influence these events during normal and disease progression.

Arch Gynecol Obstet. 2012 May 5. [Epub ahead of print]

Endometriosis: a premenopausal disease? Age pattern in 42,079 patients with endometriosis.

Haas D, Chvatal R, Reichert B, Renner S, Shebl O, Binder H, Wurm P, Oppelt P.

Source

Department of Obstetrics and Gynecology, Linz General Hospital, Krankenhausstrasse 9, 4021, Linz, Austria.

Abstract

PURPOSE:

The objectives of this study were to examine the age distribution among women suffering from endometriosis and to establish that endometriosis is not a disease that occurs only in premenopausal women. The null hypothesis was that there are also postmenopausal women with endometriosis.

METHODS:

In a retrospective epidemiological study, a descriptive analysis of data from the Federal Statistical Office in Germany for 2005 and 2006 was carried out. A total of 42,079 women in Germany were admitted for surgical treatment due to histologically confirmed endometriosis during this period. The patients’ age distribution was examined and they were assigned to 5-year age groups and then to premenopausal, perimenopausal, and postmenopausal subgroups.

RESULTS:

A total of 20,835 women in 2005 and 21,244 in 2006 were admitted to hospital for the treatment of endometriosis. In the premenopausal group (age 0-45 years), there were 33,814 patients (80.36 %); 23 patients (0.05 %) in this premenopausal group were younger than 15. There were 7,191 patients (17.09 %) in the perimenopausal group (45-55 years), and the postmenopausal group (55-95 years) included 1,074 patients (2.55 %).

CONCLUSIONS:

The assumption that endometriosis is a disease of the premenopausal period and in women of reproductive age needs to be called into question, as well as the influence of estrogen in fully developed endometriosis. Due to the relatively high prevalence of the condition in patients aged over 40, physicians should consider endometriosis in cases of unclear pelvic pain in this age group.

Gynecol Endocrinol. 2012 May 4. [Epub ahead of print]

Endometriosis in a rural remote setting: a cross-sectional study.

Somigliana E, Vigano P, Benaglia L, Crovetto F, Vercellini P, Fedele L.

Source

Doctors with Africa CUAMM , Padova , Italy.

Abstract

Women in Western nations are exposed to an “unnatural” high number of menstrual cycles and this has been claimed to favour the development of endometriosis. If so, the prevalence of the disease should be low in remote rural settings characterized by high fertility rate, frequent teen-age pregnancy and protracted breast-feeding. To verify this hypothesis, we investigated the prevalence of endometriosis among women referring to the District Hospital of Aber, Northern Uganda for gynecological complaints. Subjects were considered affected if they had a history of surgery for endometriosis or if they had a positive clinical or ultrasound examination. Overall, a total of 528 gynecological consultancies were performed during the one year study period. Endometriosis was recorded in only one case. The frequency of the disease in the whole cohort of referred cases was thus 0.2% (95% confidence intervals (CI): 0.01-0.9%). When focusing on non-pregnant women in their reproductive age, it was 0.3% (95% CI: 0.01-1.3%). When considering women complaining symptoms suggestive for endometriosis, it was 0.4% (95% CI: 0.02-1.9%). In conclusion, endometriosis is rare in a community characterized by high fertility rate, frequent teen-age pregnancy and protracted breast-feeding, supporting the idea that the reproductive pattern plays a crucial role in the pathogenesis of the disease.

Reprod Sci. 2012 May 3. [Epub ahead of print]

The Expression and Functionality of Transient Receptor Potential Vanilloid 1 in Ovarian Endometriomas.

Liu J, Liu X, Duan K, Zhang Y, Guo SW.

Abstract

Pains of various kinds-dysmenorrhea, chronic pelvic pain, and dyspareunia-are the major complaints from women with endometriosis, representing the most debilitating nature of the disease. Despite extensive research, our understanding as how endometriosis causes pain is still fragmentary. In this study, we examined transient receptor potential vanilloid 1 (TRPV1)-positive nerve fibers in ectopic endometrium from women with ovarian endometriomas and in endometrium from women without endometriosis and correlated the density with the severity of dysmenorrhea in cases. We also performed an immunohistochemistry analysis of TRPV1 in ectopic and control endometrium. After finding TRPV1 immunoreactivity in ectopic endometrial cells, we further examined whether TRPV1 is functional in ectopic endometrial stromal cells (EESCs). We found that the density of TRPV1-positive nerve fibers in ectopic endometrial implants is higher than that in control endometrium and correlates positively with the severity of dysmenorrhea in women with endometriosis. In addition, TRPV1 expression was also found to be elevated significantly in EESCs when stimulated with inflammatory mediators such as prostaglandin E2 (PGE(2) ) and tumor necrosis factor-α (TNF-α). Finally, we found that TRPV1 activation can induce the release of nitric oxide (NO) and interleukin 1β (IL-1β) in EESCs. The latter finding appears to be consistent with the reports of increased TRPV1 protein expression following peripheral inflammation. Our results suggest that the increased TRPV1-positive nerve fibers may integrate various stimuli on peripheral terminals or primary sensory neurons and generate hyperalgesia in endometriosis. The expression and functionality of TRPV1 in EESCs also suggest that TRPV1 may have neurosecretory functions that are yet to be elucidated.

Acta Obstet Gynecol Scand. 2012 May;91(5):605-12. doi: 10.1111/j.1600-0412.2012.01370.x. Epub 2012 Mar 29.

Transvaginal color Doppler sonography predicts ovarian interstitial fibrosis and microvascular injury in women with ovarian endometriotic cysts.

Qiu JJ, Liu MH, Zhang ZX, Chen LP, Yang QC, Liu HB.

Source

Department of Obstetrics and Gynecology, Second Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China.

Abstract

OBJECTIVE:

To determine novel predictors of ovarian interstitial fibrosis and microvascular injury associated with ovarian endometriotic cysts (OECs).

DESIGN:

Case-control study.

SETTING:

The gynecology unit of an affiliated hospital in China.

POPULATION:

Women <40 years of age with OECs or benign ovarian tumors (controls).

METHODS:

Transvaginal color Doppler sonography was performed preoperatively to detect ovarian interstitial flow. Postoperatively, expressions of transforming growth factor-β1 (TGF-β1) and thrombospondin-1 (TSP-1), as well as microvessel density in ovarian interstitial, were analyzed using immunohistochemistry.

MAIN OUTCOME AND MEASURES:

Ovarian interstitial flow and expressions of TGF-β1, TSP-1, and microvessel density.

RESULTS:

Compared with controls, ovarian interstitial flow in the study group was decreased and arterial spectra indicated significantly higher resistance indices. Microvessel density was reduced, but TGF-β1 and TSP-1 were elevated in the study group. There was a positive correlation between TGF-β1 and TSP-1. There were negative correlations between TGF-β1 and microvessel density, and between TSP-1 and microvessel density. Microvessel density and resistance indices were negatively correlated, whereas the correlations of TGF-β1 and TSP-1 with resistance indices were positive.

CONCLUSIONS:

Resistance indices are consistent with pathological indices. Changes in resistance indices in ovaries with endometriosis are related to interstitial fibrosis and microvascular injury.

Acta Radiol. 2012 May 1;53(4):473-7. Epub 2012 Mar 15.

T2* relaxometry mapping of the uterine zones.

Imaoka I, Nakatsuka T, Araki T, Katsube T, Okada M, Kumano S, Ishii K, Ashikaga R, Okuaki T, Van Cauteren M, Murakami T.

Source

Department of Radiology, Kinki University Faculty of Medicine, Osaka, Japan. iizumi@med.kindai.ac.jp

Abstract

BACKGROUND:

Previous literature demonstrated that the T2* value of the uterine junctional zone was lower than that of peripheral myometrium by using BOLD MR imaging. We expect T2* mapping image may add more information to T2-weighted images of the uterine myometrium.

PURPOSE:

To evaluate whether T2* mapping software would reproduce the result of previous report, and to apply the software to benign uterine diseases.

MATERIAL AND METHODS:

Five healthy volunteers and 19 patients clinically suspected of having benign pelvic disease were imaged using a 1.5T MR system. All women were of reproductive age, and all provided informed consent. Sagittal T2* images using a multishot EPI sequence were obtained. T2* values were calculated and color T2* maps reconstructed using a T2* fitting tool.

RESULTS:

The uterine zones could be identified in all 24 examinations on the T2* maps. In addition, a thin “4th zone” was seen between the endometrium and the JZ (junctional zone) in 19 of 24 examinations. The T2* value of JZ was significantly lower than that of peripheral myometrium (PM) (P < 0.001). No significant difference in the T2* value of the JZ or of PM was noted between normal uterus and uterus with leiomyomas and/or adenomyosis.

CONCLUSION:

A quantitative T2* map can easily be obtained using the PRIDE software T2* fitting tool, and the software reproduces the result from previous report. T2* value of the junctional zone was lower than that of peripheral myometrium regardless of having benign myometrial diseases.

Am J Pathol. 2012 May;180(5):1781-6. Epub 2012 Mar 5.

Genetic polymorphisms of DNMT3L involved in hypermethylation of chromosomal ends are associated with greater risk of developing ovarian endometriosis.

Borghese B, Santulli P, Héquet D, Pierre G, de Ziegler D, Vaiman D, Chapron C.

Source

Department of Gynecology and Obstetrics 2, Cochin University Hospital, Paris Descartes University, Public Hospitals of Paris (AP-HP), Paris, France. bruno.borghese@inserm.fr

Abstract

Endometrioma is a common ovarian cyst associated with pain and infertility, but its pathogenesis remains enigmatic. Demonstration of the subtelomeric location of hypermethylation in endometrioma has been reported by genome-wide profiling of methylated promoters. Recently, rs113593938, a polymorphism in the DNA methyltransferase 3-like (DNMT3L) gene has been associated with subtelomeric hypomethylation. We investigated the association between endometrioma and rs113593938, rs8129776, rs7354779, and rs2276248, which were chosen for thoroughly covering the locus of interest. We enrolled 127 patients with histologically proved endometrioma and no associated deep endometriotic lesions and 317 healthy subjects for a case-control genetic association study. Genotyping was performed after PCR amplification of the region encompassing the polymorphisms, restriction enzyme digestion, and detection of fragments on an agarose gel. Differences in genotype and allele distributions between cases and controls were tested for each polymorphism separately using the χ(2) test. The rs8129776 was significantly associated with endometrioma (P = 0.003). Haplotype analysis showed a higher risk for the patients carrying the ACCC+T haplotypes for rs8129776, rs7354779, rs113593938, and rs2276248 (odds ratio, 7.15; 95% CI, 2.63 to 19.44). We report, for the first time to our knowledge, the association of DNMT3L genetic variants and endometrioma; DNMT3L expression itself was not modified. Our study constitutes a first milestone toward a plausible role of DNMT3L in the establishment of specific DNA methylation patterns in endometrioma.

Am J Surg Pathol. 2012 May;36(5):688-95.

Endometriosis does not confer improved prognosis in ovarian carcinoma of uniform cell type.

Cuff J, Longacre TA.

Source

Department of Surgical Pathology, Stanford University School of Medicine, CA 94305, USA. longacre@stanford.edu

Abstract

The role of endometriosis in ovarian cancer, disease progression, and survival is a subject of active investigation. A series of 144 ovarian cancers with clear cell or endometrioid histology or associated endometriosis, all classified on the basis of strict histologic criteria, was evaluated to further explore the relationship between endometriosis-associated ovarian cancer and age at presentation, FIGO stage, histology, presence of synchronous primary disease elsewhere in the mullerian tract, and survival. Patients with endometrioid carcinomas were significantly younger (mean, 52 y) in comparison with patients with either clear cell carcinoma (mean, 55 y) or mixed tumors (mean, 59 y; P=0.002). Clear cell carcinoma presented as low-stage disease (FIGO I) in 33% of cases compared with endometrioid carcinomas in 97% of cases and mixed carcinomas in 27% of cases. Endometriosis was associated with 53% of clear cell carcinomas, 33% of endometrioid carcinomas, and 45% of mixed tumors (P<0.001). Synchronous primary tumors, observed in 31% of endometrioid tumors, 5% of mixed tumors, and in 2% of clear cell tumors (P<0.001), were unlikely to be associated with endometriosis (P=0.04). Univariate analysis of the aggregate cohort demonstrated that the single best overall predictor of disease-free survival was FIGO stage at presentation (P<0.001), followed by histologic subtype (P=0.003). Endometriosis did not have a significant relationship with disease-free survival (P=0.7). We conclude that the link between endometriosis and ovarian cancer is much stronger for clear cell carcinoma than for other histologic subtypes (P<0.001). Furthermore, when uniform histologic criteria are applied, true mixed endometrioid and clear cell carcinomas are uncommon; most endometriosis-associated mixed tumors are heterogenous mixtures of endometrioid, mucinous, and serous histology with areas of clear cell cytoplasm. Endometriosis per se does not appear to predict prognosis in clear cell and endometrioid tumors, with the possible exception of tumors with mixed histology. Until more data are collected, pathologists should classify ovarian tumors with mixed histology as a separate and potentially unique biological and prognostic group.

Arch Gynecol Obstet. 2012 May;285(5):1483-6. Epub 2011 Dec 25.

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

Ulukus M, Yeniel AÖ, 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.

Arch Gynecol Obstet. 2012 May;285(5):1307-12. Epub 2011 Nov 8.

Performance of peripheral (serum and molecular) blood markers for diagnosis of endometriosis.

Mabrouk M, Elmakky A, Caramelli E, Farina A, Mignemi G, Venturoli S, Villa G, Guerrini M, Manuzzi L, Montanari G, De Sanctis P, Valvassori L, Zucchini C, Seracchioli R.

Source

Reproductive Medicine Unit, S. Orsola-Malpighi Hospital, via Massarenti 9, 40138 Bologna, Italy.

Abstract

PURPOSE:

To quantify the mRNA levels of MMP-3, MMP-9, VEGF and Survivin in peripheral blood and the serum levels of CA-125 and Ca19-9 in women with and without endometriosis and to investigate the performance of these markers to differentiate between deep and ovarian endometriosis.

METHODS:

A case control study enrolled a series of 60 patients. Twenty controls have been matched with 20 cases of ovarian and 20 cases of deep endometriosis. Univariable and multivariable performance of serum CA125 and CA19-9, mRNA for Survivin, MMP9, MMP3 and VEGF genes have been evaluated by means of ROC curves and logistic regression, respectively.

RESULTS:

No difference in markers’ concentration was detected between ovarian and deep endometriosis. In comparison with controls, serum CA125 and CA19 yielded the better sensitivity followed by mRNA for Survivin gene (81.5, 51.9 and 7.5% at 10% false positive rate, respectively). Multivariable estimated odds of endometriosis yielded a sensitivity of 87% at the same false positive rate.

CONCLUSIONS:

A combination of serum and molecular markers could allow a better diagnosis of endometriosis.

Arch Gynecol Obstet. 2012 May;285(5):1487-8. Epub 2011 Nov 6.

The investigation of ABO and Rh blood groups distribution in patients with endometriosis needs new project design.

Tabei SM, Daliri K, Amini A.

Abstract

We carefully studied all the three published papers in your journal as “ABO and Rh Blood group distribution in patients with endometriosis” and “Associations of ABO blood groups with various gynecologic diseases” and would like to express our point of view about them.

Comment on

Autoimmun Rev. 2012 May;11(6-7):A471-8. Epub 2011 Dec 2.

Ovarian failure and polycystic ovary syndrome.

Petríková J, Lazúrová I.

Source

1st Department of Internal Medicine, Medical Faculty of P. J. Šafárik University, Košice, Slovakia.

Abstract

The human ovary is commonly the target of an autoimmune attack leading to the ovarian dysfunction which can be manifested as premature ovarian failure (POF), polycystic ovary syndrome (PCOS), unexplained infertility as well as endometriosis. In case of POF, the evidence for an autoimmune etiology is based on the presence of lymphocytic oophoritis, autoantibodies to ovarian antigens and association with other autoimmune disorders, which was clearly documented in many studies. The search for antiovarian antibodies has been undertaken in numerous studies, especially in patients with POF, however their results are still conflicting particularly due to difference in laboratory methods as well as many ovarian components being potential antigens. On the other side the autoimmune etiology of PCOS is still debated and was documented in some cases. Association of PCOS with non-organ specific autoimmune disorders is controversial; however association with autoimmune thyroid disease was well demonstrated in some studies.

Clin Chem. 2012 May;58(5):936-40. Epub 2011 Dec 28.

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.

Comment in

Environ Health Prev Med. 2012 May 1. [Epub ahead of print]

Lack of an association human dioxin detoxification gene polymorphisms with endometriosis in Japanese women: results of a pilot study.

Matsuzaka Y, Kikuti YY, Goya K, Suzuki T, Cai LY, Oka A, Inoko H, Kulski JK, Izumi SI, Kimura M.

Source

Division of Basic Molecular Science and Molecular Medicine, School of Medicine, Tokai University, Bohseidai, Isehara, Kanagawa, 259-1193, Japan, yasunari.matsuzaka@helmholtz-muenchen.de.

Abstract

OBJECTIVES:

Endometriosis is a chronic disease caused by the presence of endometrial tissue in ectopic locations outside the uterus. Chronic exposure to the environmental pollutant dioxin has been correlated with an increased incidence in the development of endometriosis in non-human primates. We have therefore examined whether there is an association between the polymorphisms of ten dioxin detoxification genes and endometriosis in Japanese women.

METHODS:

This was a pilot study in which 100 patients with endometriosis and 143 controls were enrolled. The prevalence of five microsatellite and 28 single nucleotide polymorphism markers within ten dioxin detoxification genes (AhR, AHRR, ARNT, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTP1, GSTT1, NAT2) was examined.

RESULTS:

Taking into account that this analysis was a preliminary study due to its small sample size and genetic power, the results did not show any statistically significant difference between the cases and controls for any of the allele and genotype frequency distributions examined. In addition, no significant associations between the allele/genotype of all polymorphisms and the stage (I-II or III-IV) of endometriosis were observed.

CONCLUSION:

Based on the findings of this pilot study, we conclude the polymorphisms of the ten dioxin detoxification genes analyzed did not contribute to the etiology of endometriosis among our patients.

Eur J Endocrinol. 2012 May;166(5):765-78. Epub 2012 Jan 24.

Vitamin D and fertility: a systematic review.

Lerchbaum E, Obermayer-Pietsch B.

Source

Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria. elisabeth.lerchbaum@medunigraz.at

Abstract

BACKGROUND:

Vitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence that in addition to sex steroid hormones, the classic regulators of human reproduction, vitamin D also modulates reproductive processes in women and men.

AIM:

The aim of this review was to assess the studies that evaluated the relationship between vitamin D and fertility in women and men as well as in animals.

METHODS:

We performed a systematic literature search in Pubmed for relevant English language publications published until October 2011.

RESULTS AND DISCUSSION:

The vitamin D receptor (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. Vdr knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Moreover, we present evidence that vitamin D is involved in female reproduction including IVF outcome (clinical pregnancy rates) and polycystic ovary syndrome (PCOS). In PCOS women, low 25-hydroxyvitamin D (25(OH)D) levels are associated with obesity, metabolic, and endocrine disturbances and vitamin D supplementation might improve menstrual frequency and metabolic disturbances in those women. Moreover, vitamin D might influence steroidogenesis of sex hormones (estradiol and progesterone) in healthy women and high 25(OH)D levels might be associated with endometriosis. In men, vitamin D is positively associated with semen quality and androgen status. Moreover, vitamin D treatment might increase testosterone levels. Testiculopathic men show low CYP21R expression, low 25(OH)D levels, and osteoporosis despite normal testosterone levels.

Eur J Obstet Gynecol Reprod Biol. 2012 May;162(1):96-101. Epub 2012 Feb 28.

Association between endometriosis and polymorphisms in insulin-like growth factor binding protein genes in Korean women.

Kim H, Ku SY, Kim SH, Choi YM, Kim JG.

Source

Department of Obstetrics and Gynecology, Incheon Medical Center, Incheon, Republic of Korea.

Abstract

OBJECTIVE:

Genetic factors are known to be associated with the development and progression of endometriosis, but the genes related to endometriosis have not been defined. Insulin-like growth factor binding proteins (IGFBPs) are believed to be involved in the proliferation and apoptosis of cells that play an important role in the pathophysiologic mechanism of endometriosis. This study aimed to determine the association between endometriosis and polymorphisms of the IGFBP genes in Korean women.

STUDY DESIGN:

In a case-control study, the rs1995051, rs1065780 and c.759A>G single nucleotide polymorphisms (SNPs) in the IGFBP1 gene and the -672A>G, -202A>C and c.95C>G SNPs in the IGFBP3 gene were analyzed in 128 women with endometriosis and 108 normal control women.

RESULTS:

The haplotype genotype composed of a combination of three IGFBP1 gene polymorphisms was not related to endometriosis, while the haplotype genotype of the IGFBP3 gene had a significant association with endometriosis. Women not carrying the AAG (-672A/-202A/c.95G) haplotype allele of three IGFBP3 gene polymorphisms have a 3.19-times higher risk of endometriosis compared with women with AAG homozygotes, and this trend was found in women with advanced endometriosis but not in women with early endometriosis.

CONCLUSIONS:

The AAG haplotype allele of the -672A>G, -202A>C and c.95C>G polymorphisms in the IGFBP3 gene may be associated with advanced endometriosis in Korean women.

Eur J Obstet Gynecol Reprod Biol. 2012 May;162(1):87-90. Epub 2012 Feb 27.

Diameter of dominant leiomyoma is a possible determinant to predict coexistent endometriosis.

Isono W, Wada-Hiraike O, Osuga Y, Yano T, Taketani Y.

Source

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

Abstract

OBJECTIVE:

To identify the frequency and assess risk factors for unexpected discovery of peritoneal endometriotic implants in patients who underwent myomectomy or hysterectomy for symptomatic uterine leiomyomas.

STUDY DESIGN:

We retrospectively collected medical records of 829 patients with symptomatic leiomyomas in The University of Tokyo Hospital. All the patients underwent abdominal or laparoscopic surgeries between January 2001 and December 2010 and the presence or absence of endometriosis during surgery was analyzed. Possible determinant to predict coexistent endometriosis was statistically investigated.

RESULTS:

In total, 105 leiomyoma cases (12.7% in 829 patients) were diagnosed with endometriosis. Patients with small dominant leiomyomas were significantly complicated by peritoneal endometriotic implants (small leiomyomas were classified as < 8 cm). The patients with both diagnoses were more likely to be infertile and at age 39 years or younger than those with leiomyoma alone.

CONCLUSIONS:

Women undergoing myomectomy or hysterectomy with both endometriosis and leiomyomas have several different clinical features compared with women with only leiomyomas. The size of largest leiomyoma may provide an important clue for coexistent endometriosis. Women with substantial infertility despite a smaller leiomyomas burden may be more likely to have a surgical indication for concomitant endometriosis.

Fertil Steril. 2012 May;97(5):1028-32.

Defective endometrial receptivity.

Revel A.

Source

Department of Obstetrics and Gynecology, Hadassah University Hospital, Jerusalem, Israel. arielr2@hadassah.org.il

Abstract

The endometrium is one of the most fascinating tissues in the human body. Its sole purpose is to enable implantation of an embryo during a relatively short window of opportunity in the menstrual cycle. It is becoming clear that overcoming the current bottleneck in improvements to assisted reproductive techniques will require a closer look at the interface between uterus and embryo. Indeed, embryo implantation requires a cross talk with a receptive endometrium. Using sonography, hysteroscopy and endometrial biopsy we can learn about anatomical and functional markers of endometrial receptivity. This article reviews the factors which might cause defective endometrial receptivity. These include uterine polyps, septa, leiomyomata and adhesions. The effect of thin endometrium, endometriosis and hydrosalpinx is also described. Finally contemporary investigation of molecular markers of endometrial receptivity is described. Improving embryo implantation by a closer look inside the uterus is the key to increasing pregnancy rates in IVF.

Fertil Steril. 2012 May;97(5):1143-51.e1-3. Epub 2012 Mar 14.

Glutathione transferase polymorphisms and risk of endometriosis associated with polychlorinated biphenyls exposure in Italian women: a gene-environment interaction.

Vichi S, Medda E, Ingelido AM, Ferro A, Resta S, Porpora MG, Abballe A, Nisticò L, De Felip E, Gemma S, Testai E.

Source

Department of Environment and Primary Prevention, Unit of Mechanisms of Toxicity, Italian National Institute for Health, Rome, Italy.

Abstract

OBJECTIVE:

To investigate the occurrence of a gene-environment interaction between glutathione transferase (GST) gene polymorphisms (GSTM1, GSTT1, GSTP1, and GSTA1) and serum polychlorinated biphenyls (PCBs) levels. This is suggested as possible risk factors for endometriosis, a multifactorial gynecological disease.

DESIGN:

Case-control study conducted from 2002 to 2005.

SETTING:

Policlinico Umberto I, “Sapienza” University of Rome and Italian National Institute for Health, Rome.

PATIENT(S):

Italian women (N = 343), with laparoscopic diagnosis and histologic confirmation of the presence (cases, N = 181) or the absence (controls, N = 162) of endometriosis.

INTERVENTION(S):

Genomic DNA extraction, multiplex polymerase chain reaction (PCR), and restriction fragment length polymorphism analysis. Determination of serum concentrations of selected PCBs by ion-trap mass spectrometry (subgroup, 63 cases and 63 controls).

MAIN OUTCOME MEASURE(S):

Endometriosis diagnosis by laparoscopy, GST genotypes, serum PCB levels.

RESULT(S):

The genotype distributions of GSTM1, GSTA1, and GSTP1 did not show any statistically significant difference between cases and controls. The GSTT1 null genotype was negatively associated with the disease. The GSTP1 wild-type genotype in the presence of medium-high blood levels of PCB153, total PCBs, or of high levels of PCB180 significantly increased the risk of endometriosis, suggesting a multiplicative interaction.

CONCLUSION(S):

The GSTs polymorphisms per se do not increase the risk of developing endometriosis. However, a gene-environment interaction was observed for GSTP1(Ile/Ile) and GSTM1 null genotypes, modulating the effect of PCB153, PCB180, and of total PCBs on disease risk.

Fertil Steril. 2012 May;97(5):1129-35.e1. Epub 2012 Feb 24.

Increased expression of macrophage colony-stimulating factor and its receptor in patients with endometriosis.

Budrys NM, Nair HB, Liu YG, Kirma NB, Binkley PA, Kumar S, Schenken RS, Tekmal RR.

Source

Department of Obstetrics and Gynecology, University of Texas Health Science Center, San Antonio, Texas 78229, USA.

Abstract

OBJECTIVE:

To investigate the expression and regulation of colony-stimulating factor 1 (CSF-1) and its receptor, C-FMS, in endometriosis.

DESIGN:

In vivo and vitro study.

SETTING:

University-based academic medical center.

PATIENT(S):

Reproductive-age women undergoing surgery for benign conditions.

INTERVENTION(S):

Peritoneal and endometrial tissue samples were obtained.

MAIN OUTCOME MEASURE(S):

CSF-1 and C-FMS expression.

RESULT(S):

Significantly higher CSF-1 levels were found in peritoneal fluid of patients with endometriosis compared with control subjects. Ectopic endometriotic tissue had 3.5-fold and 1.7-fold increases in CSF-1 and C-FMS expression, respectively, compared with eutopic tissue. Coculture of endometrial cells from either established cell lines or patient samples with peritoneal mesothelial cells (PMCs) led to increased expression of CSF-1 and C-FMS. A higher but nonsignificant increase in levels of C-FMS and CSF-1 was found in cocultures of endometrial epithelial cells from patients with endometriosis compared with those without endometriosis.

CONCLUSION(S):

Increased CSF-1 levels may contribute to endometriosis lesion formation and progression. Elevation in CSF-1 after coculture of endometrial cells with PMCs suggests that endometrial tissue may be a source of peritoneal CSF-1. Increased C-FMS expression in endometrial cells from women with endometriosis cocultured with PMCs suggests that endometrial tissue involved in lesion formation is highly responsive to CSF-1 signaling.

Fertil Steril. 2012 May;97(5):1124-8. Epub 2012 Feb 16.

Genetic association study of polymorphisms FOXP3 and FCRL3 in women with endometriosis.

Barbosa CP, Teles JS, Lerner TG, Peluso C, Mafra FA, Vilarino FL, Christofolini DM, Bianco B.

Source

Human Reproduction and Genetics Center, Department of Gynecology and Obstetrics, Faculdade de Medicina do Santo André, São Bernardo do Campo and São Caetano do Sul County, Santo André, Brazil.

Abstract

OBJECTIVE:

To consider a possible cumulative effect of two genetic polymorphisms (FOXP3 C-2383T/rs3761549 and FCRL3 C-169T/rs7528684) that were previously shown to be associated with endometriosis.

DESIGN:

Genetic association study.

SETTING:

Human reproduction outpatient clinic of Faculdade de Medicina do ABC.

PATIENT(S):

One hundred eighty-eight infertile women with endometriosis and 169 controls.

INTERVENTION(S):

Detection of polymorphisms FOXP3 (C-2383T/rs3761549) and FCRL3 (C-169T/rs7528684) by TaqMan real-time polymerase chain reaction. The results were analyzed statistically.

MAIN OUTCOME MEASURE(S):

Genotype distribution, allele frequency, and combination analysis of the FOXP3 and FCRL3 polymorphisms.

RESULT(S):

Single-marker analysis revealed a significant association of FOXP3 C-2383T and FCRL3 C-169T, independently, with endometriosis-related infertility, regardless of the stage of the disease. Considering the combined genotypes of FCRL3 and FOXP3 polymorphisms, a positive association was found between genotypes FCRL3TT/FOXP3CT, FCRL3CT/FOXP3CT, and FCRL3CC/FOXP3CT and the risk of endometriosis development. Moreover, a progression of the disease risk was observed according to the presence of one or two copies of risk allele FCRL3 C and only one copy of risk allele FOXP3 T (odds ratio [OR] = 2.14, OR = 3.25, and OR = 6.0, respectively, for genotypes FCRL3TT/FOXP3CT, FCRL3CT/FOXP3CT, and FCRL3CC/FOXP3CT).

CONCLUSION(S):

Our findings support a possible gene-gene interaction leading to a cumulative effect on endometriosis development.

Gynecol Obstet Fertil. 2012 May;40(5):320-5. Epub 2012 Apr 20.

Medical treatment of endometriosis: An obligation rather than a mere option!

[Article in French]

Roman H, Sanguin S, Puscasiu L.

Source

Clinique gynécologique et obstétricale, CHU de Rouen, 1, rue de Germont, 76031 Rouen, France; Groupe de recherche EA 4308 « spermatogenèse et qualité des gamètes », université de Rouen, 76000 Rouen, France.

Abstract

The aim of this article is to argue the usefulness of the systematic administration of medical treatment in women managed for endometriosis, either alone or associated with the surgery. The authors dispute seven frequent objections against the medical treatment: the lack of curative effect, the lack of primary prevention and the risk of delaying the diagnostic, the contraceptive effect in women wishing to conceive, the adverse effects, the risk of occurence of new lesions following the arrest of the treatment, the lack of proof favourable to the efficient prevention of recurrences and the cost of the treatment. The authors conclude that to date the therapeutic amenorrhea represents an indispensable tool in the management of the endometriosis, in women both benefiting or not from surgical procedures.

Gynecol Surg. 2012 May;9(2):131-137. Epub 2011 Dec 28.

Is adenomyosis the neglected phenotype of an endomyometrial dysfunction syndrome?

Brosens I, Kunz G, Benagiano G.

Abstract

Since the dissociation between adenomyoma and endometriosis in the 1920s and the laparoscopic progress in the diagnosis and surgery of endometriosis, the literature has been greatly focused on the disease endometriosis. The study of adenomyosis, on the other hand, has been neglected as the diagnosis remained based on hysterectomy specimens. However, since the introduction of magnetic resonance and sonographic imaging techniques in the 1980s, the myometrial junctional zone has been identified as a third uterine zone and interest in adenomyosis was renewed. This has also been the start for the interest in the role of the myometrial junctional zone dysfunction and adenomyosis in reproductive and obstetrical disorders.

Hum Pathol. 2012 May;43(5):720-5. Epub 2011 Sep 22.

CDC42-positive macrophages may prevent malignant transformation of ovarian endometriosis.

Canet B, Pons C, Espinosa I, Prat J.

Source

Department of Pathology, Hospital de la Santa Creu i Sant Pau, Institute of Biomedical Research (IIB Sant Pau), Autonomous University of Barcelona, Barcelona -08041, Spain.

Abstract

It is currently thought that most clear cell and endometrioid carcinomas arise from ovarian endometriosis. We recently suggested that, besides their origin in the ovary, reduction of CDC42 messenger RNA (a member of the RHO GTPase family) may contribute to explain why clear cell carcinomas are not uncommonly found limited to the ovary (stage I). On the other hand, little is known about the expression of CDC42 in ovarian endometriosis with and without carcinoma. Twenty-two endometriotic cysts not associated with carcinoma, 19 endometriotic cysts associated with carcinoma (contiguous endometriosis), as well as the 19 corresponding tumors (11 clear cell, 4 endometrioid, and 4 mixed-clear cell and endometrioid-carcinomas) were investigated. We analyzed CDC42 expression both by real-time polymerase chain reaction and immunohistochemistry. Endometriotic cysts not associated with carcinoma showed higher expression of CDC42 messenger RNA than cysts associated with carcinoma (P = .002). Immunohistochemically, CDC42 was exclusively expressed by macrophages. CDC42-positive macrophages were present in most of the endometriotic cysts not associated with carcinoma (11/19, or 58%). In contrast, only 5 endometriotic cysts containing carcinoma (contiguous endometriosis) (5/18, or 28%) and 1 ovarian carcinoma arising from endometriosis (1/18, or 5%) had CDC42-positive macrophages (58% versus 28%, P = .065; 28% versus 5%, P = .046). Our results raise the possibility that CDC42-positive macrophages may prevent the development of endometrioid and clear cell carcinomas.

 

 

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