Pag. 6

 

Eur J Obstet Gynecol Reprod Biol. 2012 May 23. [Epub ahead of print]

Association between TGF-β1-509C/T polymorphism and endometriosis: a systematic review and meta-analysis.

Zhang F, Yang Y, Wang Y.

Source

School of Public Health and Health Management, Chongqing Medical University, Chongqing, China.

Abstract

OBJECTIVE:

To evaluate the association between the transforming growth factor β1 gene-509C/T (TGF-β1-509C/T) polymorphism and the risk of endometriosis.

STUDY DESIGN:

Relevant studies published before October 2011 were identified by searching PubMed and Embase. Studies were selected using prior defined criteria. The strength of the relationship between the TGF-β1-509C/T polymorphism and endometriosis risk was assessed by Odds Ratios (ORs). Fixed- or random-effects model was calculated according to study heterogeneity. Stratification analysis and sensitivity analysis were also conducted. Possible publication bias was tested by funnel plots and Egger’s test.

RESULTS:

Of 49 potentially relevant studies, six case-control studies were identified in this meta-analysis. The integrated result showed that the TGF-β1-509C/T polymorphism was not associated with the endometriosis risk for the allele contrast (T vs. C: OR=1.57, 95%CI=0.88-2.79), the additive genetic model (T/T vs. C/C: OR=2.96, 95%CI=0.97-9.10), the dominant genetic model (T/T+T/C vs. C/C: OR=1.80, 95%CI=0.80-4.07) and the recessive genetic model (T/T vs. C/C+T/C: OR=1.91, 95%CI=0.89-4.12). In the stratified analysis by ethnicity, genotyping method and source of control, no significantly association was found. Publication bias was not detected in the included studies.

CONCLUSIONS:

Meta-analyses of the available data showed that the association between TGF-β1-509C/T polymorphism and susceptibility of endometriosis was not significant. More studies are needed to elucidate its role in endometriosis.

Endocrinology. 2012 May 22. [Epub ahead of print]

Raf-1, a Potential Therapeutic Target, Mediates Early Steps in Endometriosis Lesion Development by Endometrial Epithelial and Stromal Cells.

De La Garza EM, Binkley PA, Ganapathy M, Krishnegowda NK, Tekmal RR, Schenken RS, Kirma NB.

Source

Department of Obstetrics and Gynecology (E.M.D.L.G., P.A.B., M.G., N.K.K., R.R.T., R.S.S., N.B.K.), University of Texas Health Science Center at San Antonio and Cancer Therapy and Research Center (R.R.T., N.B.K.), San Antonio, Texas 78229.

Abstract

Endometriosis is a hormone-sensitive gynecological disorder characterized by the benign growth of endometrial-like tissue in the pelvic cavity. Endometriotic lesions composed of endometrial stromal cells (ESC) and glandular epithelial cells (EEC) are thought to arise from menstrual endometrial tissue reaching the pelvic cavity via retrograde menstruation. The cause of endometriotic lesion formation is still not clear. Recent evidence suggest that cytokines may play a role in the early development of endometriosis lesions. Because cytokines and growth factors signal via the Raf-1 kinase pathway, we have examined the role of Raf-1 in early steps of endometriosis lesion formation, specifically attachment of endometrial cells to peritoneal mesothelial cells (PMC) and invasion of endometrial cells through PMC (trans-mesothelial invasion). Raf-1 antagonist GW5074 decreased attachment to PMC and trans-mesothelial invasion by primary EEC and ESC. Raf-1 also mediated TGFβ-induced trans-mesothelial invasion by the established, low-invasive EEC line EM42. TGFβ treatment of EEC resulted in Raf-1 phosphorylation at S338 and phosphorylation of ERK, suggesting that TGFβ activates Raf-1 signaling in these cells. GW5074 had little effect on ESC proliferation but inhibited EEC growth significantly under reduced serum conditions. Antagonizing Raf-1 activity and expression via GW5074 and specific Raf-1 small interfering RNA, respectively, did not alter EEC resistance to growth inhibition by TGFβ. Raf-1 inhibition blocked induction of EEC growth by epidermal growth factor. Our data suggest that Raf-1 may mediate pathologic steps involved in early endometriosis lesion formation and may be a mediator of TGFβ and epidermal growth factor actions in endometriosis.

Hum Pathol. 2012 May 22. [Epub ahead of print]

Involvement of pelvic inflammation-related mismatch repair abnormalities and microsatellite instability in the malignant transformation of ovarian endometriosis.

Fuseya C, Horiuchi A, Hayashi A, Suzuki A, Miyamoto T, Hayashi T, Shiozawa T.

Source

Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.

Abstract

Inflammation in the ovary, including ovulation and pelvic inflammatory disease, has been proposed to play a role in the pathogenesis of ovarian cancer. Endometriotic lesions trigger a local inflammatory reaction and have been reported to be associated with an increased risk of epithelial ovarian cancer. However, the precise molecular mechanisms of ovarian cancer arising from endometriosis are still to be elucidated. To clarify the involvement of mismatch repair (MMR) abnormalities in the inflammation-associated malignant transformation of endometriosis, the immunohistochemical expression of mismatch repair proteins (human mutL homolog 1 [hMLH1] and human mutS homolog 2 [hMSH2]) was examined in 27 cases of ovarian endometriosis, 25 cases of ovarian carcinoma accompanied by endometriosis, and 39 cases of solitary ovarian carcinoma. In addition, the relationship between mismatch repair abnormalities including the microsatellite instability, PTEN (phosphatase and tensin homolog) mutation, and clinicopathologic parameters was analyzed. The expression of mismatch repair proteins was stepwisely decreased in endometriosis, ovarian carcinoma accompanied by endometriosis, and ovarian carcinoma. Tumors harboring multiple microsatellite instability (high-frequency microsatellite instability [MSI-H]) were detected in 4 (14.8%) of 27 cases of endometriosis and 7 (30.4%) of 23 cases of ovarian carcinomas. The frequency of PTEN mutations was higher in MSI-H cases than in microsatellite instability-stable (MSI-S) cases. In 2 cases of ovarian carcinoma accompanied by endometriosis, the decreased expression of mismatch repair proteins and MSI-H was observed in both the endometriosis and carcinoma lesions. Clinicopathologically, the MSI-H cases were associated with elevated serum levels of C-reactive protein and higher white blood cell counts. These findings suggest that mismatch repair abnormalities might be involved in the malignant transformation of ovarian endometriosis and that inflammation induces mismatch repair abnormalities during ovarian carcinogenesis arising from endometriosis.

Mol Hum Reprod. 2012 May 21. [Epub ahead of print]

RNAi-mediated blocking of ezrin reduces migration of ectopic endometrial cells in endometriosis.

Jiang QY, Xia JM, Ding HG, Fei XW, Lin J, Wu RJ.

Source

Department of Obstetrics and Gynecology, Women’s Hospital, School of Medicine, Zhejiang University, No. 1 Xueshi Road, Hangzhou, Zhejiang Province 310006, People’s Republic of China.

Abstract

Ezrin is a member of the ezrin-radixin-moesin (ERM) family of membrane-cytoskeletal linkage proteins. It is important for maintenance of cell shape, adhesion, migration and division. The overexpression of ezrin in some tumours is associated with increased cell migration that is mediated by the Rho/ROCK family of small GTPases. To investigate the role of ezrin in the migration of ectopic endometrial cells in endometriosis, we conducted real-time quantitative RT-PCR analysis of the eutopic and ectopic endometrium from women with endometriosis compared with those without the disease. RNAi, wound healing assays and western blot analysis of endometriotic cells were also included in this research. We found significantly higher levels of mRNA expression of ezrin (0.42 versus 0.27, P < 0.05), RhoA (0.99 versus 0.74, P < 0.05), RhoC (0.79 versus 0.43, P < 0.005) and ROCK1 (0.68 versus 0.38, P < 0.005) in the ectopic endometrial cells compared with the eutopic endometrial cells in endometriosis. Blocking ezrin with small-interfering RNA reduced the migration of ectopic endometrial cells with decreased expression of RhoA (42.68%), RhoC (58.42%) and ROCK1 (59.88%). Our results indicate that the over-expression of ezrin in endometriosis may play a significant role in the migration of endometrial cells of endometriosis, and the RhoC/Rock pathway may provide a promising treatment target.

Ugeskr Laeger. 2012 May 21;174(21):1459-1460.

Atypical course of Budd-Chiari syndrome with hydrothorax.

[Article in Danish]

Bilenko A, Mahdi B.

Source

Morgenfruevænget 1, 5270 Odense N. [email protected]

Abstract

Budd-Chiari syndrome is a very rare condition with an incidence and a prevalence of respectively 0.8 and 1.4 per million inhabitants per year. Significant large right-sided pleural effusion without significant ascites is well-known in portal hypertension and cirrhosis, where it occurs in 5-10% of the patients. Due to the presence of endometriosis and the dominant symptom in the form of hydrothorax up to 5 l per day delayed the correct diagnosis in a case with a 33 year-old woman. Reviews of the initially performed computed tomographies could have been made shortly after admission thus avoiding long time illness and hospitalization.

Eur J Obstet Gynecol Reprod Biol. 2012 May 19. [Epub ahead of print]

Association of endometriosis risk and genetic polymorphisms involving biosynthesis of sex steroids and their receptors: an updating meta-analysis.

Hu X, Zhou Y, Feng Q, Wang R, Su L, Long J, Wei B.

Source

School of Public Health, Guangxi Medical University, Nanning, People’s Republic of China.

Abstract

The objective of our study is to assess the association of endometriosis risk and genetic polymorphisms involving biosynthesis of sex steroids and their receptors. A systematic search of three databases was conducted. Twenty-seven studies on the association of the cytochrome P450 subfamily 17 (CYP17), estrogen receptor gene (ER), progesterone receptor gene (PR), 17-beta-hydroxysteroid dehydrogenase type 1 gene (HSD17B1), and cytochrome P450 subfamily 19 (CYP19) polymorphisms with endometriosis risk were identified. When all groups were pooled, we found an association between HSD17B1 (A variant allele vs. G wild allele: odds ratio (OR)=1.42, 95% confidence interval (CI)=1.10-1.84, P=0.007) and PR (P2 variant allele vs. P1 wild allele, OR=1.43, 95% CI=0.99-2.08, P=0.058) polymorphisms and endometriosis risk, while failing to detect links with CYP17, ER, and CYP19 polymorphisms examined. In the subgroup analysis, a significant association of CYP17 and ERα-PvuII polymorphisms with endometriosis was found neither in a Caucasian population nor in an Asian population. The findings of our study suggest that HSD17B1 and PR polymorphisms are associated with an increased risk of endometriosis. Further investigation into the association between CYP17, ER, PR, HSD17B1, and CYP19 polymorphisms and endometriosis risk is warranted and should include larger sample sizes.

Eur J Med Res. 2012 May 18;17(1):12. [Epub ahead of print]

DNA hypomethylation of the COX-2 gene promoter is associated with up-regulation of its mRNA expression in eutopic endometrium of endometriosis.

Wang D, Chen Q, Zhang C, Ren F, Li T.

Abstract

ABSTRACT:

BACKGROUND:

Accumulated evidence reveals that cyclooxygenase-2 (COX-2) was overexpressed in eutopic endometrium of endometriosis, which may play a critical role in the pathogenesis of endometriosis. However, few studies have been performed to explore the molecular mechanisms underlying the abnormal high expression of COX-2 in endometriosis. Considering the fact that a number of recent studies have shown DNA methylation affecting some genes in endometriosis, the present study was therefore aimed to determine whether the observed high expression COX-2 in endometriosis is caused by the hypomethylation of CpG island within the promoter of this gene.

METHODS:

The endometrial tissues were collected from 60 women with endometriosis (endometriosis group) and 20 women without endometriosis (control group). The methylation status of COX-2 was examined by methylation specific PCR. Quantitative real-time RT-PCR was performed to measure COX-2 mRNA level in endometrial tissues.

RESULTS:

The frequency of promoter hypermethylation of COX-2 was lower in eutopic endometrium of the endometriosis group (41.7%) than that in the control group (75.0%), P < 0.05. COX-2 mRNA level in the eutopic endometrium of the endometriosis group was 2.61-fold higher than that in the control group (P < 0.01). COX-2 mRNA level in unmethylated endometrium of the endometriosis group or the control group was 2.39-fold and 2.66-fold, respectively, higher than that in the methylated endometrium of the same group (P < 0.01).

CONCLUSIONS:

The hypomethylation within the promoter of COX-2 may be responsible for the elevated gene expression in eutopic endometrium of endometriosis.

Fertil Steril. 2012 May 17. [Epub ahead of print]

Expression of phosphoinositide-specific phospholipase C enzymes in normal endometrium and in endometriosis.

Lo Vasco VR, Leopizzi M, Chiappetta C, Businaro R, Polonia P, Rocca CD, Litta P.

Source

Department of Sensitive Organs, Policlinic Umberto I, Sapienza University, Rome, Italy.

Abstract

OBJECTIVE:

To delineate the panel of expression of phosphoinositide-specific phospholipase C (PI-PLC) signaling enzymes in normal endometrium and in endometriosis.

DESIGN:

Clinical/experimental study.

SETTING:

University.

PATIENT(S):

Healthy donor woman and endometriosis-affected woman.

INTERVENTION(S):

Normal endometrium and endometriosis surgical biopsies were analyzed using gene expression analyses methodology (reverse transcriptase-polymerase chain reaction [PCR], bioanalyses).

MAIN OUTCOME MEASURE(S):

Gene expression (messenger RNA concentration) measures of 12 PI-PLC enzymes: PI-PLC β1, PI-PLC β2, PI-PLC β3, PI-PLC β4, PI-PLC γ1, PI-PLC γ2, PI-PLC δ1, PI-PLC δ3, PI-PLC δ4, PI-PLC ε, PI-PLC η1, and PI-PLC η2.

RESULT(S):

PI-PLC β1, PI-PLC β3, PI-PLC δ1, and PI-PLC δ3 enzymes were detected, although differently expressed in normal and endometriosis tissues.

CONCLUSION(S):

The involvement of PI-PLC enzymes in inflammation and the consistency of susceptible endometriosis loci with PI-PLC genes mapping corroborate the hypothesis that PI signaling might be involved in the pathogenesis of endometriosis.

Gynecol Endocrinol. 2012 May 17. [Epub ahead of print]

A potential link of oxidative stress and cell cycle regulation for development of endometriosis.

Shigetomi H, Higashiura Y, Kajihara H, Kobayashi H.

Source

Department of Obstetrics and Gynecology, Nara Medical University , Nara , Japan.

Abstract

Background: The roles of molecular alteration such as genomic instability and cell survival are debated aspects of the pathogenesis of endometriosis. To review the contemporary literature on potential factors and their signaling pathways that support prolonged survival of endometriotic cells. Methods: This article reviews the English-language literature for molecular, pathogenetic, and pathophysiological studies on endometriosis. This review is focused on the association of hepatocyte nuclear factor (HNF)-1β with endometriosis. Results: The iron-induced oxidative stress plays a fundamental role for the pathogenesis of endometriosis. Oxidative stress, secondary to influx of iron during retrograde menstruation, modifies lipids and proteins, leading to cell and DNA damage. Recent studies demonstrated HNF-1β overexpression in endometriotic foci. HNF-1β increases the survival of endometriotic cells under iron-induced oxidative stress conditions possibly through the activation of forkhead box (FOX) transcription factors and/or endometriosis-specific expression of microRNAs. Endometriotic cells expressing HNF-1β also display cell cycle checkpoint pathways required to survive DNA damaging events. Conclusions: HNF-1β in endometriosis might be a factor that controls the cell cycle and DNA damage checkpoints.

J Pharmacol Sci. 2012 May 17;119(1):40-51. Epub 2012 Apr 28.

Protease-activated receptor-stimulated interleukin-6 expression in endometriosis-like lesions in an experimental mouse model of endometriosis.

Shinohara A, Kutsukake M, Takahashi M, Kyo S, Tachikawa E, Tamura K.

Source

Department of Endocrine Pharmacology, Tokyo University of Pharmacy and Life Sciences, Japan.

Abstract

The present study was undertaken to investigate the function of protease-activated receptor (PAR) in endometriotic lesions using a mouse model of endometriosis. Unilateral ovariectomy (uOVX) was performed on female nude mice followed by intraperitoneal transplantation of a suspension mixture of immortalized human endometrial epithelial cells (EM-1) and stromal cells (EtsT-499). Endometriosis-like lesions were observed mostly around the dissection site after transplantation. The expression of interleukin (IL)-6 and cyclooxygenase-2 in the lesions was enhanced in uOVX mice compared to non-uOVX animals. In non-uOVX mice, IL-6 mRNA levels were higher in lesions formed with cells that were pretreated with PAR1/2 agonists (thrombin, 10 U/ml and PAR2-activating peptide, 30 µM) compared to untreated, intact cells. Peritoneal IL-6 concentrations were also increased in the PAR1/2 agonists-treated group. IL-6 expression induced by PAR activation was blocked by the treatment of cells with serine protease inhibitors. In cultured endometrial cells, simultaneous treatment with PAR1 and PAR2 agonists significantly increased the expression of IL-6. These results suggest that peritoneal bleeding may accelerate IL-6 expression in endometriotic lesions in part through the activation of PAR.

Cochrane Database Syst Rev. 2012 May 16;5:CD006568.

Chinese herbal medicine for endometriosis.

Flower A, Liu JP, Lewith G, Little P, Li Q.

Source

ComplementaryMedicine ResearchUnit, Dept PrimaryMedical Care, Southampton University, Ringmer, UK. [email protected]

Abstract

BACKGROUND:

Endometriosis is characterized by the presence of tissue that is morphologically and biologically similar to normal endometrium in locations outside the uterus. Surgical and hormonal treatment of endometriosis have unpleasant side effects and high rates of relapse. In China, treatment of endometriosis using Chinese herbal medicine (CHM) is routine and considerable research into the role of CHM in alleviating pain, promoting fertility, and preventing relapse has taken place.This review is an update of a previous review published in the Cochrane Database of Systematic Reviews 2009, issue No 3.

OBJECTIVES:

To review the effectiveness and safety of CHM in alleviating endometriosis-related pain and infertility.

SEARCH METHODS:

We searched the Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library) and the following English language electronic databases (from their inception to 31/10/2011): MEDLINE, EMBASE, AMED, CINAHL, and NLH.We also searched Chinese language electronic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Sci & Tech Journals (VIP), Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), and Chinese Medical Current Contents (CMCC).

SELECTION CRITERIA:

Randomised controlled trials (RCTs) involving CHM versus placebo, biomedical treatment, another CHM intervention; or CHM plus biomedical treatment versus biomedical treatment were selected. Only trials with confirmed randomisation procedures and laparoscopic diagnosis of endometriosis were included.

DATA COLLECTION AND ANALYSIS:

Risk of bias assessment, and data extraction and analysis were performed independently by three review authors. Data were combined for meta-analysis using relative risk (RR) for dichotomous data. A fixed-effect statistical model was used, where appropriate. Data not suitable for meta-analysis were presented as descriptive data.

MAIN RESULTS:

Two Chinese RCTs involving 158 women were included in this review. Both these trials described adequate methodology. Neither trial compared CHM with placebo treatment.There was no evidence of a significant difference in rates of symptomatic relief between CHM and gestrinone administered subsequent to laparoscopic surgery (95.65% versus 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). The intention-to-treat analysis also showed no significant difference between the groups (RR 1.04, 95% CI 0.91 to 1.18). There was no significant difference between the CHM and gestrinone groups with regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT).CHM administered orally and then in conjunction with a herbal enema resulted in a greater proportion of women obtaining symptomatic relief than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). Overall, 100% of women in all the groups showed some improvement in their symptoms.Oral plus enema administration of CHM showed a greater reduction in average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90, 95% CI -4.55 to -1.25; P < 0.01). Combined oral and enema administration of CHM also showed a greater improvement measured as the disappearance or shrinkage of adnexal masses than with danazol (RR 1.70, 95% CI 1.04 to 2.78). For lumbosacral pain, rectal discomfort, or vaginal nodules tenderness, there was no significant difference between CHM and danazol.

AUTHORS’ CONCLUSIONS:

Post-surgical administration of CHM may have comparable benefits to gestrinone but with fewer side effects. Oral CHM may have a better overall treatment effect than danazol; it may be more effective in relieving dysmenorrhoea and shrinking adnexal masses when used in conjunction with a CHM enema. However, more rigorous research is required to accurately assess the potential role of CHM in treating endometriosis.

Update of

Am J Reprod Immunol. 2012 May 15. doi: 10.1111/j.1600-0897.2012.01151.x. [Epub ahead of print]

Cyclooxygenase-2 ( COX -2) Gene-765G/C Polymorphism and Advanced-Stage Endometriosis in Korean Women.

Kim HY, Cho S, Choi YS, Yang HI, Lee KE, Seo SK, Lee BS.

Source

Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Abstract

PROBLEM:

We investigated the association of COX -2 gene-765G/C polymorphism and risk of advanced-stage endometriosis in Korean women.

METHOD OF STUDY:

This study consisted of 268 women with advanced-stage endometriosis and 242 control women without endometriosis in Korea. Subjects were genotyped for the -765G/C polymorphism of the COX -2 gene by RFLP-PCR analysis.

RESULTS:

There were significant differences in the genotype distributions of the -765G/C polymorphism between patients with advanced-stage endometriosis and control subjects. The C allele for -765G/C was associated with significantly lower risk of advanced-stage endometriosis (OR, 0.14; 95% CI, 0.06-0.30).

CONCLUSIONS:

We have demonstrated a significant genetic association between the -765G/C polymorphism and advanced-stage endometriosis in Korean women. The -765C allele may be protective against the development of the disease in Korean women.

Genet Mol Res. 2012 May 15;11(2):1401-8.

Association of TP53 gene codon 72 polymorphism with endometriosis in Mexican women.

Gallegos-Arreola MP, Figuera-Villanueva LE, Puebla-Pérez AM, Montoya-Fuentes H, Suarez-Rincon AE, Zúñiga-González GM.

Source

Molecular Medicine Department, Biomedical Research Center West, Instituto Mexicano del Seguro Social, Guadalajara, México [email protected]

Abstract

The TP53 tumor suppressor gene plays an important role in cell cycle regulation; polymorphisms of this gene have been associated with endometriosis. We examined the role of TP53 codon 72 polymorphism by comparing genotypes of 235 healthy Mexican women (controls with surgically excluded endometriosis) with the genotypes of 151 Mexican women with endometriosis. The observed genotype frequencies for controls and endometriosis patients were 8 and 22% for proline/proline (Pro/Pro), 30 and 34% for proline/arginine (Pro/Arg), and 62 and 44% for arginine/arginine (Arg/Arg), respectively. We found that odds ratio (OR) = 3.3; 95% confidence intervals (95%CI) = 1.7-6.4; P = 0.0001. The association was also evident in the comparison of the distributions of genotypes Pro/Pro and Pro/Arg in patients with moderate-to-severe endometriosis; OR = 1.9; 95%CI = 0.95-3.9; P = 0.049. We suggest that genotype Pro/Pro of codon 72 polymorphism in TP53 contributes significantly to endometriosis susceptibility in the Mexican population.

Gynecol Oncol. 2012 May 15. [Epub ahead of print]

Unraveling the two entities of endometrioid ovarian cancer: A single center clinical experience.

Mangili G, Bergamini A, Taccagni G, Gentile C, Panina P, Viganò P, Candiani M.

Source

Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milano, Italy.

Abstract

OBJECTIVE:

Due to the increasing prevalence of the benign condition, ovarian carcinoma arising from endometriosis is emerging as a relevant clinical entity with an unclear biological signature. We have investigated clinical and histologic features of endometriosis-associated endometrioid ovarian cancer using an institutional retrospective database.

METHODS:

Patients diagnosed with endometrioid ovarian cancer at our institution were divided into two groups according to the fulfillment or not of Sampson’s and Scott’s criteria for the detection of endometriosis-associated ovarian cancer. Clinical and histological data were reported and compared. Survival analysis was obtained using the log-rank test in an unadjusted Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model to establish independent factors associated with endometriosis-associated endometrioid ovarian cancer and to identify predictors of survival. The degree of concordance was evaluated by Cohen’s Kappa measures.

RESULTS:

Patients with endometriosis-associated endometrioid ovarian cancer were significantly younger, had a lower disease stage (62% vs 23%; p=0.003), a less prevalent high grade tumor (38% vs 82%; p=0.002) and a higher prevalence of squamous and mucinous metaplasia. The rate of endometrial cancer diagnosis was significantly higher in women with endometriosis-associated endometrioid ovarian cancer (33%) than in other patients (11%) (p=0.04) with a 92% concordance between ovarian and endometrial histologic tumor grade. A significant difference in survival rate could not be demonstrated between patients with or without endometriosis.

CONCLUSIONS:

The analysis of a retrospective endometrioid ovarian cancer database may allow to suggest a 40 molecular, morphological and clinical parallelism between endometrial and endometrioid ovarian cancers.

Fertil Steril. 2012 May 10. [Epub ahead of print]

Analysis of follicular fluid and serum markers of oxidative stress in women with infertility related to endometriosis.

Prieto L, Quesada JF, Cambero O, Pacheco A, Pellicer A, Codoceo R, Garcia-Velasco JA.

Source

Department of Obstetrics and Gynecology, La Paz Hospital, Madrid, Spain.

Abstract

OBJECTIVE:

To study the levels of four markers of oxidative stress in follicular fluid (FF) and plasma of patients with infertility related to endometriosis and controls.

DESIGN:

Experimental study.

SETTING:

University-affiliated hospital and infertility center.

PATIENT(S):

Ninety-one infertile women were included in the study (23 infertile women with endometriosis and 68 controls including infertile women due to tubal factor, male factor, or healthy egg donors).

INTERVENTION(S):

Blood was obtained at the time of egg retrieval, and FF from the mature follicles of each ovary was centrifuged and frozen until analysis.

MAIN OUTCOME MEASURE(S):

Vitamin C and E, malondialdehyde, and superoxide dismutase concentrations in plasma and follicular fluid.

RESULT(S):

Women with endometriosis showed a lower vitamin C concentration in FF (12.7 ± 5.9 vs. 9.7 ± 6.9 μg/mL) and lower superoxide dismutase concentration in plasma (0.9 ± 1.4 vs. 0.5 ± 0.7 U/mL) compared with controls. Vitamin E plasma levels were significantly higher in women with endometriosis (8.1 ± 3.8 vs. 5.2 ± 3.2 μg/mL). A nonsignificant trend toward a lower plasma concentration of malondialdehyde was found in women with endometriosis.

CONCLUSION(S):

These findings suggest a lower antioxidant capacity in infertile women with endometriosis. Although a certain level of reactive oxygen species is required under physiological conditions, an altered balance between pro-oxidant and antioxidant activities may have an impact on folliculogenesis and adequate embryo development.

Fertil Steril. 2012 May 10. [Epub ahead of print]

Effect of letrozole on estradiol production and P450 aromatase messenger RNA expression of cultured luteinized granulosa cells from women with and without endometriosis.

Lu X, Wu Y, Gao XH, Wang YW, Wang L, Sun XX.

Source

Reproductive Medical Center, International Peace Maternity and Child Health Hospital Affiliated, Shanghai Jiao Tong University, Shanghai, People’s Republic of China.

Abstract

OBJECTIVE:

To compare the estradiol production and P450 aromatase messenger RNA (mRNA) expression of cultured luteinized granulosa cells and the effect of letrozole on these parameters between women with and without endometriosis.

DESIGN:

In vitro assays.

SETTING:

Reproductive medical center.

PATIENT(S):

Patients undergoing in vitro fertilization (IVF): 23 patients with endometriosis and 19 controls without endometriosis.

INTERVENTION(S):

Luteinized granulosa cells examined for estradiol levels and P450 aromatase mRNA expression in conditioned media at different letrozole concentrations of 0.0, 0.1, 1.0, and 10.0 μmol/L.

MAIN OUTCOME MEASURE(S):

Estradiol levels of the conditioned medium measured with an enzyme-linked immunosorbent assay (ELISA) kit and P450 aromatase mRNA expression determined by quantitative reverse transcription-polymerase chain reaction (QT RT-PCR).

RESULT(S):

The estradiol concentration of the conditioned media and P450 aromatase mRNA expression in the endometriosis group were statistically significantly lower than that of the control group, irrespective of letrozole concentrations. A statistically significant reduction of these two parameters was observed in both endometriosis and control groups at letrozole concentrations of 1 μmol/L and 10 μmol/L, but there were no statistically significant differences between letrozole concentrations of 1 μmol/L and 10 μmol/L. The number of high-quality embryos in the endometriosis group was statistically significantly lower than that of the control group.

CONCLUSION(S):

Lower estradiol production and P450 aromatase mRNA expression of cultured granulosa cells were found in women with endometriosis. Letrozole in the conditioned media further reduced these parameters.

Arch Gynecol Obstet. 2012 May 9. [Epub ahead of print]

Visual pain mapping in endometriosis.

Renner SP, Boosz AS, Burghaus S, Maihöfner C, Beckmann MW, Fasching PA, Jud SM.

Source

Department of Gynecology and Obstetrics, Erlangen University Hospital, Friedrich-Alexander University of Erlangen-Nuremberg, Universitätsstrasse 21-23, 91054, Erlangen, Germany, [email protected]

Abstract

PURPOSE:

To construct pain maps in order to describe the distribution of pelvic pain in a group of endometriosis patients and endometriosis-free patients, to assess the feasibility of this method.

METHODS:

A total of 159 patients with pelvic pain who were scheduled for diagnostic laparoscopy.

RESULTS:

A total of 117 patients with and 42 patients without endometriosis were included. The pain distribution between these two patient groups appeared to differ in some peripheral anatomical structures. In the endometriosis patients, the pain was most frequently located in the rectouterine pouch.

CONCLUSIONS:

In endometriosis patients, pain mapping to assess preoperative pain sensations relative to the anatomic location of endometriotic lesions is feasible. The pain provoked by vaginal examination is frequently perceived as median relative to the actual anatomic location of the endometriotic lesions. Several anatomic and neurophysiological factors may explain this phenomenon.

Reprod Sci. 2012 May 9. [Epub ahead of print]

The G-Protein Coupled Estrogen Receptor (GPER) is Expressed in Normal Human Ovaries and is Upregulated in Ovarian Endometriosis and Pelvic Inflammatory Disease Involving the Ovary.

Heublein S, Lenhard M, Vrekoussis T, Schoepfer J, Kuhn C, Friese K, Makrigiannakis A, Mayr D, Jeschke U.

Abstract

Estrogens play a crucial role in maintaining ovarian function. Deregulation of estrogen signals is associated with fertility-impairing disorders. The aim of this study was to investigate whether the G-protein-coupled estrogen receptor (GPER) is present in the human ovary. Additionally, we analyzed the folliculogenesis and ovarian endometriosis in GPER expression. Seventy-nine patients (ovarian endometriosis, n = 26; ovarian pelvic inflammatory disease [PID], n = 10; normal ovaries/endometrium, n = 30/13) were analyzed by immunohistochemistry. Normal ovaries were also assessed by real-time polymerase chain reaction and double immunofluorescence. The most intense expression of GPER was noted in the ovarian surface epithelium. Theca cells and oocytes were also significantly positive. Expression of GPER was more frequent in mature follicles/oocytes than in primordial ones, implying that GPER could be a selector during folliculogenesis. Moreover, GPER was upregulated in ovarian endometriosis and PID. Overexpression of GPER in both inflammation and endometriosis affecting the ovary may prove useful in explaining/predicting the main endometriosis-related symptoms.

J Minim Invasive Gynecol. 2012 May 8. [Epub ahead of print]

Adhesion Prevention in Endometriosis: A Neglected Critical Challenge.

Somigliana E, Vigano P, Benaglia L, Busnelli A, Vercellini P, Fedele L.

Source

Fondazione Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy.

Abstract

Prevention of adhesions, whether de novo or by re-formation, is one of the most important and surprisingly neglected aspect of the treatment of endometriosis. Adhesions may cause infertility, dyspareunia, chronic pelvic pain but also intestinal obstruction and complications at subsequent surgery. They may play a role in the development of some forms of the disease such as ovarian endometriomas and possibly also deep invasive nodules. Three randomized controlled trials have been published documenting some partial success with Interceed, Oxiplex/AP gel or Adept solution in reducing adhesions extent at second look laparoscopy performed a few weeks after initial surgery. However, data on relevant long-term outcomes such as fertility, pelvic pain or disease recurrences or other adhesions-related complications is lacking. Noteworthy, endometriosis is a chronic inflammatory disorder and the insult causing adhesions is expected to persist after surgery. Therefore preventing adhesion formation with exclusively agents at the time of surgery may be insufficient. Future studies should focus on a 2-step strategy that includes measures applied at the time of surgery and subsequent administration of agents able to prevent the development of new adhesions.

J Obstet Gynaecol Res. 2012 May 8. doi: 10.1111/j.1447-0756.2011.01834.x. [Epub ahead of print]

Xanthogranulomatous salpingitis and oophoritis associated with endometriosis and uterine leiomyoma presenting as intestinal obstruction.

Abeysundara PK, Padumadasa GS, Tissera WG, Wijesinghe PS.

Source

Department of Obstetrics and Gynaecology, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.

Abstract

Xanthogranulomatous inflammation is a rare form of chronic granulomatous inflammation. Bacterial infections, immunosuppression, chronic inflammatory conditions, luminal obstruction, endometriosis, leiomyoma, abnormal lipid metabolism, ineffective antibiotic therapy, ineffective clearance of bacteria by phagocytes and chronic irritation of the urachal remnant have been implicated in the pathogenesis. There are very few reported cases of xanthogranulomatous salpingitis and oophoritis. We present such a case in a 34-year-old female, with primary subfertility for eight years, endometriosis, uterine leiomyoma, type II diabetes mellitus and a history of surgery for endometriosis and fibroids and surgical wound infection, who presented with symptoms of intestinal obstruction. The patient underwent emergency laparotomy followed by total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histology revealed xanthogranulomatous salpingitis and oophoritis. Chronic inflammation due to inadequate treatment of bacterial infection, coupled with pelvic endometriosis and uterine leiomyoma may have led to xanthogranulomatous salpingitis and oophoritis.

 

 

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