Pag. 9

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. flower.power@which.net.

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 patrici0803@yahoo.com.mx.

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, stefan.renner@uk-erlangen.de.

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.

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 13-19years, 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±1168.53pg/mL vs 62.96±82.35pg/mL), TNF-α (5.79±5.60pg/mL vs 1.68±1.24pg/mL) and glycodelin A (94.24±60.97ng/mL vs 53.52±41.43ng/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 (90.00pg/mL), TNF-α (3.00pg/mL) and glycodelin A (60.0ng/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 3.00pg/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 3years 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.

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