Pag. 10

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.

Hum Reprod.2012 May;27(5):1292-9. Epub 2012 Mar 14.

The burden of endometriosis: costs and quality of life of women with endometriosis and treated in referral centres.

Simoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I, Brodszky V, Canis M, Colombo GL, DeLeire T, Falcone T, Graham B, Halis G, Horne A, Kanj O, Kjer JJ, Kristensen J, Lebovic D, Mueller M, Vigano P, Wullschleger M, D’Hooghe T.

Source

Katholieke Universiteit Leuven, Leuven, Belgium.

Abstract

BACKGROUND:

This study aimed to calculate costs and health-related quality of life of women with endometriosis-associated symptoms treated in referral centres.

METHODS:

A prospective, multi-centre, questionnaire-based survey measured costs and quality of life in ambulatory care and in 12 tertiary care centres in 10 countries. The study enrolled women with a diagnosis of endometriosis and with at least one centre-specific contact related to endometriosis-associated symptoms in 2008. The main outcome measures were health care costs, costs of productivity loss, total costs and quality-adjusted life years. Predictors of costs were identified using regression analysis.

RESULTS:

Data analysis of 909 women demonstrated that the average annual total cost per woman was €9579 (95% confidence interval €8559-€10 599). Costs of productivity loss of €6298 per woman were double the health care costs of €3113 per woman. Health care costs were mainly due to surgery (29%), monitoring tests (19%) and hospitalization (18%) and physician visits (16%). Endometriosis-associated symptoms generated 0.809 quality-adjusted life years per woman. Decreased quality of life was the most important predictor of direct health care and total costs. Costs were greater with increasing severity of endometriosis, presence of pelvic pain, presence of infertility and a higher number of years since diagnosis.

CONCLUSIONS:

Our study invited women to report resource use based on endometriosis-associated symptoms only, rather than drawing on a control population of women without endometriosis. Our study showed that the economic burden associated with endometriosis treated in referral centres is high and is similar to other chronic diseases (diabetes, Crohn’s disease, rheumatoid arthritis). It arises predominantly from productivity loss, and is predicted by decreased quality of life.

Hum Reprod.2012 May;27(5):1445-50. Epub 2012 Mar 12.

Diagnostic value of serum activin A and follistatin levels in women with peritoneal, ovarian and deep infiltrating endometriosis.

Reis FM, Luisi S, Abrão MS, Rocha AL, Viganò P, Rezende CP, Florio P, Petraglia F.

Source

Department of Obstetrics and Gynecology, University of Minas Gerais, and National Institute of Hormones and Women’s Health, Belo Horizonte, Brazil.

Abstract

BACKGROUND:

Activin A is a growth factor, produced by the endometrium, whose actions are modulated by the binding protein follistatin. Both proteins are detectable in the peripheral serum and their concentrations may be increased in women with endometriosis. The present study was designed to evaluate whether serum levels of activin A and follistatin are altered, and therefore have a potential diagnostic value, in women with peritoneal, ovarian and deep infiltrating endometriosis.

METHODS:

We performed a multicenter controlled study evaluating simultaneously serum activin A and follistatin concentrations in women with and without endometriosis. Women with endometriosis (n = 139) were subdivided into three groups: peritoneal endometriosis (n = 28); ovarian endometrioma (n = 61) and deep infiltrating endometriosis (n = 50). The control group (n = 75) consisted of healthy women with regular menstrual cycles. Blood samples were collected from a peripheral vein and assayed for activin A and follistatin using commercially available enzyme immunoassay kits.

RESULTS:

The ovarian endometrioma group had serum activin A levels significantly higher than healthy controls (0.22 ± 0.01 ng/ml versus 0.17 ± 0.01 ng/ml, P < 0.01). None of the endometriosis groups had serum follistatin levels which were significantly altered compared with healthy controls; however, levels found in the endometrioma group (2.34 ± 0.32 ng/ml) were higher than that in the deep endometriosis group (1.50 ± 0.17 ng/ml, P < 0.05). The area under the receiver operating characteristic curve of activin A was 0.700 (95% confidence interval: 0.605-0.794), while that of follistatin was 0.620 (95% confidence interval: 0.510-0.730) for the diagnosis of ovarian endometrioma. The combination of both markers into a duo marker index did not improve significantly their diagnostic accuracy.

CONCLUSIONS:

The present study demonstrated that serum activin A and follistatin are not significantly altered in peritoneal or deep infiltrating endometriosis and have limited diagnostic accuracy in the diagnosis of ovarian endometrioma.

Hum Reprod.2012 May;27(5):1320-6. Epub 2012 Mar 12.

Endothelial dysfunction but not increased carotid intima-media thickness in young European women with endometriosis.

Santoro L, D’Onofrio F, Campo S, Ferraro PM, Tondi P, Campo V, Flex A, Gasbarrini A, Santoliquido A.

Source

Department of Internal Medicine, Complesso Integrato Columbus, Catholic University of Rome, Via Moscati, 31, Rome 00168, Italy. lu_santoro@libero.it

Abstract

BACKGROUND:

Atherosclerosis is a chronic and degenerative disease developing typically in the elderly; nonetheless, a condition of accelerated atherosclerosis can be observed precociously in the presence of some diseases. Endometriosis, a chronic benign gynecological disorder, shows some characteristics, such as oxidative stress, systemic inflammation and a pro-atherogenic lipid profile, which could increase the risk of developing accelerated atherosclerosis. The aim of our study was to evaluate markers of subclinical atherosclerosis in young European women with endometriosis.

METHODS:

This cross-sectional study included 37 women with endometriosis and 31 control subjects. The presence of subclinical atherosclerosis was investigated by ultrasound evaluation of common carotid intima-media thickness (ccIMT) and flow-mediated dilation (FMD); in addition, serum levels of lipids, inflammatory and coagulation parameters, as well as markers of endothelial inflammation and activation, were determined.

RESULTS:

Women with endometriosis showed significantly lower values of FMD compared with controls [mean difference: -4.62, 95% confidence interval (CI): -6.52, -2.73; P < 0.001], whereas no significant differences in ccIMT values were found between the two groups. As regards markers of endothelial inflammation and activation, women with endometriosis had significantly higher values of inter-cellular adhesion molecule 1 (P < 0.001), vascular cell adhesion molecule 1 (P < 0.001), E-selectin (P < 0.001), von Willebrand factor (P = 0.004) and ristocetin cofactor (P = 0.001) compared with controls.

CONCLUSIONS:

Our study suggests that women with endometriosis have more subclinical atherosclerosis, resulting in a higher risk of developing cardiovascular disorders. Moreover, our findings demonstrate that endothelial dysfunction can occur in the absence of structural atherosclerotic changes; its evaluation might be helpful in young women with endometriosis.

Hum Reprod.2012 May;27(5):1314-9. Epub 2012 Mar 12.

Segmental bowel resection for colorectal endometriosis: is there a correlation between histological pattern and clinical outcomes?

Mabrouk M, Spagnolo E, Raimondo D, D’Errico A, Caprara G, Malvi D, Catena F, Ferrini G, Paradisi R, Seracchioli R.

Source

The Minimally Invasive Gynaecological Surgery Unit, Gynaecology Department, S.Orsola-Malpighi Hospital, University of Bologna, Via Massarenti 13, Bologna 40138, Italy.

Abstract

BACKGROUND:

Laparoscopic segmental resection as a treatment for intestinal endometriosis can be supported by favorable clinical outcomes, but carries a high risk of major complications. The purpose of this study is to evaluate histopathological patterns of colorectal endometriosis and investigate potential relationships between histological findings and clinical data.

METHODS:

We consecutively included 47 patients treated with laparoscopic segmental resection because of symptomatic colorectal endometriosis. All patients underwent follow-up for a median of 18 months (range: 6-35). We examined the histological patterns of colorectal endometriosis and evaluated the relationships between histological findings (satellite lesions, positive margins and vertical infiltration) and clinical outcomes (incidence of recurrence, quality of life and symptom improvement). Moreover, we observed if satellite lesions could influence preoperative scores of the short form-36 health survey (SF-36) questionnaire and visual analogue score (VAS) for pain symptoms.

RESULTS:

There were no statistically significant differences in terms of anatomical and pain recurrences, pain symptoms and quality of life improvement among patients with or without positive margins, satellite lesions and different degrees of vertical infiltration (P > 0.05). Furthermore, women with or without satellite lesions were no different in terms of preoperative VAS of pain symptoms and SF-36 scores (P > 0.05).

CONCLUSIONS:

The presence of satellite lesions or positive resection margins does not seem to influence clinical outcomes of segmental colorectal resection. Similarly, satellite lesions do not appear to have a major role in determining preoperative clinical presentation. These results may be useful to reconsider the surgical strategy for bowel endometriosis.

Hum Reprod.2012 May;27(5):1300-13. Epub 2012 Mar 8.

Therapeutic potential of andrographolide for treating endometriosis.

Zheng Y, Liu X, Guo SW.

Source

Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China.

Abstract

BACKGROUND:

Mounting evidence shows that nuclear factor-κB (NF-κB) plays an important role in endometriosis. We therefore evaluated the therapeutic potential of andrographolide, an NF-κB inhibitor.

METHODS:

Primary cell cultures were performed using ectopic endometrial tissue specimens and their homologous eutopic endometrial specimens from 16 women with endometriosis, as well as control samples from 4 women without endometriosis. Andrographolide was evaluated for an effect on cell proliferation and cell cycle, DNA-binding activity of NF-κB and expression of cyclooxygenase-2 (COX-2) and tissue factor (TF). In a rat model of endometriosis, andrographolide treatment was evaluated for an effect on lesion size, hotplate response latency and expression of phosphorylated p50 and p65, COX-2 and nerve growth factor (NGF) in ectopic endometrium.

RESULTS:

Andrographolide dose dependently suppressed proliferation and cell cycle progression, attenuated DNA-binding activity of NF-κB in endometriotic stromal cells and inhibited COX-2 and TF expression. In the rat experiment, induced endometriosis resulted in reduced response latency. Andrographolide treatment significantly reduced lesion size in a dose-dependent manner and significantly increased response latency. Andrographolide treatment also significantly reduced immunoreactivity of COX-2, phosphorylated p50 and p65, and NGF in ectopic endometrium.

CONCLUSIONS:

Treatment with andrographolide significantly suppresses the growth of ectopic endometrium in vitro and in vivo, and results in a significant improvement in generalized hyperalgesia in rats with induced endometriosis. Therefore, andrographolide may be cytoreductive and may relieve pain symptoms in women with endometriosis. With excellent safety and cost profiles, andrographolide could be a promising therapeutic agent for endometriosis.

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