Pag. 20

J Vis Exp. 2012 Jan 6;(59):e3396. doi: 10.3791/3396.

Mouse model of surgically-induced endometriosis by auto-transplantation of uterine tissue.

Pelch KE, Sharpe-Timms KL, Nagel SC.

Source

Obstetrics, Gynecology and Women’s Health and Division of Biological Sciences, University of Missouri, USA.

Abstract

Endometriosis is a chronic, painful disease whose etiology remains unknown. Furthermore, treatment of endometriosis can require laparoscopic removal of lesions, and/or chronic pharmaceutical management of pain and infertility symptoms. The cost associated with endometriosis has been estimated at 22 billion dollars per year in the United States. To further our understanding of mechanisms underlying this enigmatic disease, animal models have been employed. Primates spontaneously develop endometriosis and therefore primate models most closely resemble the disease in women. Rodent models, however, are more cost effective and readily available. The model that we describe here involves an autologous transfer of uterine tissue to the intestinal mesentery (Figure 1) and was first developed in the rat and later transferred to the mouse. The goal of the autologous rodent model of surgically-induced endometriosis is to mimic the disease in women. We and others have previously shown that the altered gene expression pattern observed in endometriotic lesions from mice or rats mirrors that observed in women with the disease. One advantage of performing the surgery in the mouse is that the abundance of transgenic mouse strains available can aid researchers in determining the role of specific components important in the establishment and growth of endometriosis. An alternative model in which excised human endometrial fragments are introduced to the peritoneum of immunocompromised mice is also widely used but is limited by the lack of a normal immune system which is thought to be important in endometriosis. Importantly, the mouse model of surgically induced endometriosis is a versatile model that has been used to study how the immune system, hormones and environmental factors affect endometriosis as well as the effects of endometriosis on fertility and pain.

J Neurol. 2012 Jan 4. [Epub ahead of print]

Sciatic endometriosis presenting as periodic (catamenial) sciatic radiculopathy.

Ghezzi L, Arighi A, Pietroboni AM, Jacini F, Fumagalli GG, Esposito A, Bresolin N, Galimberti D, Scarpini E.

Source

Department of Neurological Sciences, “Dino Ferrari” Center, Fondazione Cà Granda, IRCCS Ospedale Maggiore Policlinico, University of Milan, Milan, Italy, lauraghezzi@me.com.

Hum Pathol. 2012 Jan 3. [Epub ahead of print]

HMGA gene rearrangement is a recurrent somatic alteration in polypoid endometriosis.

Medeiros F, Wang X, Araujo AR, Erickson-Johnson MR, Lima JF, Meuter A, Winterhoff B, Oliveira AM.

Source

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

The pathogenesis of endometriosis is unclear, and several genetic, endocrine, immune, and environmental agents have been evaluated with no putative causative factors identified. Here, we show somatic genetic alterations involving HMGA1 (6p21) and HMGA2 (12q15) in 3 cases of polypoid endometriosis. The lesions involved the small bowel mesentery and perirectal soft tissue in 1 case and the posterior vaginal fornix and sigmoid colon serosa in 2 other cases, respectively. All had a polypoid configuration with cystically dilated irregular glands and fibrotic stroma, containing thick-walled vessels. Conventional cytogenetic analysis of 1 case showed 46,XX,t(5;12)(q13;q15) in all metaphases. Fluorescence in situ hybridization studies confirmed the balanced rearrangement of HMGA2. HMGA1 rearrangements were present in 2 additional cases. Rearrangements were exclusively found in the stromal component but not in the glandular component. These findings suggest that HMGA rearrangements likely contribute to the pathogenesis of endometriosis. However, additional studies are needed to better define the biologic role of this genetic alteration.

Noncyclic Chronic Pelvic Pain Therapies for Women: Comparative Effectiveness [Internet].

Editors

Andrews J, Yunker A, Reynolds WS, Likis FE, Sathe NA, Jerome RN.

Source

Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Jan. Report No.: 11(12)-EHC088-EF.
AHRQ Comparative Effectiveness Reviews.

Excerpt

OBJECTIVES:

The Vanderbilt Evidence-based Practice Center systematically reviewed evidence on therapies for women age 18 and over with noncyclic chronic pelvic pain (CPP). We focused on the prevalence of conditions thought to occur commonly with CPP; changes in pain, functional status, quality of life, and patient satisfaction resulting from surgical and nonsurgical treatment approaches; harms of nonsurgical approaches; evidence for differences in surgical outcomes if an etiology for CPP is identified postsurgery; and evidence for selecting one intervention over another after an approach fails.

DATA SOURCES:

We searched MEDLINE® via PubMed, PsycInfo®, EMBASE Drugs and Pharmacology, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases as well as the reference lists of included studies.

REVIEW METHODS:

We included studies published in English from January 1990 to May 2011. We excluded intervention studies with fewer than 50 adult women with CPP; cross-sectional studies or case series with fewer than 100 women with CPP addressing the prevalence of comorbidities; and studies lacking relevance to CPP treatment.

RESULTS:

Of 36 included studies, 18 were randomized controlled trials (RCTs) (2 good, 3 fair, and 13 poor quality); 3 were cohort studies (3 poor quality); and 15 were cross-sectional studies addressing the prevalence of comorbidities (quality varied by comorbidity). The most frequently reported comorbidities were dysmenorrhea, dyspareunia, and irritable bowel syndrome (IBS). Among studies addressing surgical interventions, there was no evidence that laparoscopic uterosacral nerve ablation (LUNA) is more effective than simple diagnostic laparoscopy and no evidence of benefit of lysis of adhesions. Evidence was insufficient to comment on relief of pain after hysterectomy. Nine studies of nonsurgical approaches assessed hormonal therapies for endometriosis-associated CPP and reported similar effectiveness among active agents. One exception was an RCT comparing raloxifene with placebo, which reported more rapid return of pain in the raloxifene group. Few studies assessed nonhormonal medical or nonpharmacologic management; benefits were reported in single studies of a pelvic physiotherapy approach, botulinum toxin, pelvic ultrasonography, and an integrated management approach. No studies provided evidence relating to a trajectory of care. Reporting of harms data was very limited.

CONCLUSIONS:

Improved characterization of the targeted condition, intervention, and population in CPP research is necessary to inform treatment choices for this commonly reported entity. A uniform definition of CPP and standardized evaluation of participants are lacking across the literature. Study populations likely vary widely, and studies may be reporting effects from treating symptoms rather than a diagnosed condition. Thus our understanding of potential treatment effects is diluted. Similarly, understanding comorbidity prevalence with CPP is difficult, as conditions may be considered part of the differential diagnosis or a concomitant condition. Among studies addressing treatment effects, little evidence demonstrates the effectiveness of surgical approaches. Studies of nonsurgical approaches typically addressed hormonal management of endometriosis-related CPP and were not placebo controlled, thus limiting our ability to understand whether hormonal therapies would be beneficial for women with CPP without endometriosis and whether pain relief is due simply to the placebo effect. Some studies reported benefits of other nonsurgical approaches, but nonhormonal and nonpharmacologic management remain understudied.

Acta Obstet Gynecol Scand. 2012 Jan;91(1):3-9. doi: 10.1111/j.1600-0412.2011.01303.x. Epub 2011 Nov 9.

Emerging indications for the levonorgestrel-releasing intrauterine system (LNG-IUS).

Heikinheimo O, Gemzell-Danielsson K.

Source

Department of Obstetrics and Gynaecology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.

Abstract

The levonorgestrel intrauterine system (LNG-IUS), originally designed for long-term contraceptive use, has been on the Scandinavian market for approximately 20 years. Novel clinical indications for the LNG-IUS, derived mainly from investigator-initiated studies, are emerging. These include heavy menstrual bleeding associated with uterine fibroids, endometriosis, adenomyosis, as well as endometrial hyperplasia. In both cohort and randomized studies, the LNG-IUS is effective in decreasing heavy menstrual bleeding, also in women diagnosed with uterine fibroids. In randomized studies the LNG-IUS has shown comparable clinical efficacy to GnRH analogues or progestins for the symptomatic treatment of endometriosis. Experience with LNG-IUS in adenomyosis is based on prospective cohort studies. Dysmenorrhea has been reported to decrease in all women, and uterine volume was seen to diminish in some of these studies. In the treatment of endometrial hyperplasias, including atypical hyperplasia, the LNG-IUS is equal or superior to treatment with systemic progestins. Further studies are needed to examine the full potential of the LNG-IUS in such common clinical situations.

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

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

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

Source

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

Abstract

OBJECTIVE:

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

MATERIALS AND METHODS:

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

RESULTS:

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

CONCLUSION:

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

Am J Obstet Gynecol. 2012 Jan;206(1):31-6. Epub 2011 Aug 22.

The utility of MRI for the surgical treatment of women with uterine fibroid tumors.

Parker WH.

Source

Department of Obstetrics and Gynecology, UCLA School of Medicine, Los Angeles, CA 90401-2831, USA. wparker@ucla.edu

Abstract

Determination of the reasonable treatment options and the appropriate clinical treatment of women with uterine fibroid tumors often depends on the ability of imaging modalities to accurately detect and localize fibroid tumors. Magnetic resonance imaging (MRI) gives the most complete evaluation (sizes, positions, number) of submucous, intramural, and subserosal myomas and is the most sensitive modality for the detection of small fibroid tumors. MRI allows the evaluation of fibroid tumor proximity to the bladder, rectum, and endometrial cavity, helps define what can be expected at surgery, and may help the gynecologist avoid missing fibroid tumors during surgery. MRI can also make the diagnosis of adenomyosis reliably and may be able to identify uterine sarcoma when present.

Am J Reprod Immunol. 2012 Jan;67(1):44-53. doi: 10.1111/j.1600-0897.2011.01063.x. Epub 2011 Aug 23.

Modulation of hepatocyte growth factor secretion in human female reproductive tract stromal fibroblasts by poly (I:C) and estradiol.

Coleman KD, Ghosh M, Crist SG, Wright JA, Rossoll RM, Wira CR, Fahey JV.

Source

Physiology Department, Dartmouth Medical School, Lebanon, NH 03756, USA.

Abstract

PROBLEM:

Hepatocyte Growth Factor (HGF) secretion facilitates epithelial cell growth and development in the female reproductive tract (FRT) and may contribute to pathological conditions such as cancer and endometriosis. We hypothesized that estradiol and poly (I:C), a synthetic RNA mimic, may have a regulatory effect on HGF secretion by stromal fibroblasts from FRT tissues.

METHOD OF STUDY:

Following hysterectomies, normal tissue from the uterus, endocervix, and ectocervix were dispersed into stromal cell fractions by enzymatic digestion and differential filtering. Stromal fibroblasts were cultured and treated with estradiol and/or poly (I:C), and conditioned media were analyzed for HGF via enzyme-linked immunosorbent assay.

RESULTS:

Treating uterine fibroblasts with estradiol or poly (I:C) significantly increased HGF secretion. When uterine fibroblasts were co-treated with estradiol and poly (I:C), the effect on HGF secretion was additive. In contrast, stromal fibroblasts from endo- and ecto-cervix were unresponsive to estradiol, but were stimulated to secrete HGF by poly (I:C).

CONCLUSION:

HGF secretion is uniquely regulated in the uterus, but not in ecto- and endo-cervix, by estradiol. Moreover, potential viral pathogens further induce HGF. These findings have potential applications in understanding both hormonal regulation of normal tissue as well as the role of HGF in tumorogenesis, endometriosis, and human immunodeficiency virus infection.

Am J Surg Pathol. 2012 Jan;36(1):117-27.

Well-differentiated papillary mesothelioma of the female peritoneum: a clinicopathologic study of 26 cases.

Malpica A, Sant’Ambrogio S, Deavers MT, Silva EG.

Source

Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. amalpica@mdanderson.org

Abstract

Well-differentiated papillary mesothelioma (WDPM) is an uncommon mesothelial tumor that occurs in the peritoneum of women over a wide age range. Although considered a tumor of uncertain malignant potential, information about its biological behavior is still limited. In this study, we present the clinicopathologic features of 26 cases of WDPM of the female peritoneum seen in our institution over a 20-year period (1990 to 2010). Clinical information and pathology material were reviewed in all cases. Patients ranged in age from 23 to 75 years (median, 47 y; mean, 48.6 y). There was no history of asbestos exposure in any of our cases. Ten patients had undergone surgery previously, and 6 had a history of endometriosis. In 24 patients, the WDPM was an incidental finding during surgery for a benign or malignant lesion. Only 2 patients presented with symptoms: 1 with an acute abdomen and the other with chronic pelvic pain. The former had developed a small hemoperitoneum because of bleeding of 1 of the lesions of WDPM, whereas the latter had a 2-cm WDPM involving the distal fallopian tube. The lesions were single or multiple (13 cases each) and ranged in size from 0.1 cm to 2 cm. The following sites were involved: abdominal or pelvic peritoneum not otherwise specified (10 cases), omentum (7 cases), cul-de-sac (6 cases), colonic serosa (4 cases), small bowel mesentery (2 cases), uterine serosa (2 cases), stomach serosa (1 case), large bowel mesentery (1 case), fallopian tube (1 case), ovary (1 case), and inguinal hernia (1 case). In all cases the lesions were excised. Microscopically, all of our cases had the typical features described for WDPM (ie, a papillary architecture that may be accompanied by glandular/tubular patterns, nests of cells and individual cells, bland mesothelial cells, absent or rare mitotic figures). The initial diagnosis in our cases was variable, including WDPM, mesothelial hyperplasia, malignant mesothelioma, serous tumor of low malignant potential of the peritoneum, papillary endosalpingiosis, and chronic xanthogranulomatous salpingiosis. Follow-up was obtained for 25 patients, and it ranged from 4 to 192 months (mean, 47.5 mo; median, 32 mo); 22 patients are alive with no evidence of WDPM after a follow-up that ranged from 5 to 144 months. One of these patients experienced recurrence of WDPM 46.5 months after initial diagnosis. In this patient, WDPM was an incidental finding during a total abdominal hysterectomy and bilateral salpingo-oophorectomy for serous cystadenofibroma. The recurrence was also an incidental finding during a colectomy for colonic adenocarcinoma. This patient is alive with no other recurrences 73 months after initial diagnosis and 36 months after diagnosis of the recurrence. Three patients died of other causes: pancreatic cancer at 4 months and 12 months and leukemia at 192 months. Recognition of the histologic features of WDPM and proper clinical correlation allow for the correct diagnosis of this entity. If necessary, immunohistochemical studies such as calretinin and keratin 5/6 facilitate the recognition of the mesothelial nature of this neoplasm. Although no patient died of disease in this series, follow-up of patients with this diagnosis is warranted on the basis of possible recurrences or misdiagnosis of an undersampled malignant mesothelioma.

Arch Gynecol Obstet. 2012 Jan;285(1):167-73. Epub 2011 Jun 17.

Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment.

Petraglia F, Hornung D, Seitz C, Faustmann T, Gerlinger C, Luisi S, Lazzeri L, Strowitzki T.

Source

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of Siena, Viale R. Bracci N. 16, 53100, Siena, Italy. petraglia@unisi.it

Abstract

PURPOSE:

To investigate the efficacy and safety of dienogest as a long-term treatment in endometriosis, with follow-up after treatment discontinuation. The study included women with endometriosis, who had previously completed a 12-week, placebo-controlled study of dienogest, who participated in an open-label extension study for up to 53 weeks. Thereafter, a patient subgroup was evaluated in a 24-week follow-up after treatment discontinuation.

METHODS:

A multicenter study performed in Germany, Italy and Ukraine. Women with endometriosis were enrolled at completion of the placebo-controlled study (n = 168). All women received dienogest (2 mg once daily, orally) and changes in pelvic pain (on a visual analog scale), bleeding pattern, adverse events and laboratory parameters were evaluated during and after treatment.

RESULTS:

The completion rate among women who entered the open-label extension study was 90.5% (n = 152). A significant decrease in pelvic pain was shown during continued dienogest treatment (P < 0.001). The mean frequency and intensity of bleeding progressively decreased. Adverse events, rated generally mild or moderate, led to withdrawal in four patients (2.4%). No clinically relevant changes in laboratory parameters were observed. During treatment-free follow-up (n = 34), the reduction in pelvic pain persisted, while bleeding frequency and intensity returned to normal patterns.

CONCLUSIONS:

Long-term dienogest showed a favorable efficacy and safety profile, with progressive decreases in pain and bleeding irregularities during continued treatment; the decrease of pelvic pain persisted for at least 24 weeks after treatment cessation.

Arch Gynecol Obstet. 2012 Jan;285(1):229-33. Epub 2011 May 19.

Clear cell adenocarcinoma of the ovary arising in atypical endometriosis: a report of eight cases.

Terada T.

Source

Department of Pathology, Shizuoka City Shimizu Hospital, Miyakami 1231, Shimizu-Ku, Shizuoka, 424-8636, Japan. piyo0111jp@yahoo.co.jp

Abstract

INTRODUCTION:

Studies of clear cell adenocarcinoma of the ovary (CCAO) arising from endometriosis are scant.

MATERIALS AND METHODS:

The author reviewed 13 cases CCAO of our pathology laboratory for the presence of endometriosis within the tumor. Eight (61.5%) of the 13 tumors contained endometriosis within the tumor. Of the eight cases, seven were atypical endometriosis and one was ordinary endometriosis. The age of the eight patients with CCAO ranged from 35 to 82 years with a median of 52 years.

RESULTS:

Grossly, the ovarian tumors of CCAO were characterized by unilocular cystic lesions containing solitary or multiple nodules in the inner surfaces. The outer surface was smooth and free of tumor. Histologically, the nodules showed typical features of pure CCAO with clear cells, hobnail cells, and hyalinized stroma. The non-nodular flat areas of the tumor were composed of a layer of atypical clear cells and endometriosis consisting of a layer of endometrial epithelium and endometrial stroma. Incipient foci of CCAO were occasionally recognized in the atypical clear cells. Seven cases with endometriosis showed atypia of the endometrial epithelium (atypical endometroiosis), and one case showed no atypia. There was contiguity between the CCAO and atypical clear cells and between atypical clear cells and endometriosis. Contiguity between atypical endometriosis and CCAO was also recognized in a few areas. The outer surface was devoid of tumor cells and endometriosis.

CONCLUSIONS:

The author speculates as follows. An endometrial cyst develops in the ovary. Its epithelium undergoes initiation, thus giving rise to atypical endometriosis consisting of dysplastic or intraepithelial neoplastic epithelium. The atypical endometriosis further undergoes initiation, leading to the atypical clear cells, and ultimately leads to CCAO showing a unilocular cyst consisting of inner masses of CCAO and flat areas composed of a layer of atypical clear cells with incipient CCAO and atypical endometriosis.

Arch Gynecol Obstet. 2012 Jan;285(1):215-21. Epub 2011 May 10.

Epigenetic inactivation of hMLH1 in the malignant transformation of ovarian endometriosis.

Ren F, Wang D, Jiang Y, Ren F.

Source

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, 36 Sanhao Street, Shenyang, 110004, China. renfang006329@163.com

Abstract

PURPOSE:

To investigate the role of epigenetic inactivation of hMLH1 during the malignant transformation of ovarian endometriosis (EMs), and to explore the relationship between the epigenetic inactivation of hMLH1 in eutopic endometria and the malignant transformation of ovarian EMs.

METHODS:

The target tissue from 29 cases of the endometriosis-associated ovarian carcinoma (EAOC) group, 20 cases of EMs group and 16 cases of control endometrium (CEs) group was obtained by laser capture microdissection (LCM). The methylation statue of hMLH1 promoter was determined by methylation-specific PCR (MSP) and the protein expression of hMLH1 was analysed by immunohistochemistry.

RESULTS:

The frequency of promoter hypermethylation of hMLH1 in the neoplastic tissue or ectopic endometria of the EAOC group was higher than that of the EMs group (p < 0.05), and the frequency of promoter hypermethylation of hMLH1 in eutopic endometria of the EAOC group was higher than that of the EMs and CEs groups (p < 0.05). In addition, the protein expression of hMLH1 in eutopic endometria of the EAOC group was lower than that of the EMs and CEs group (p < 0.05), and absence of hMLH1 protein expression was significantly correlated with promoter hypermethylation of the gene.

CONCLUSIONS:

Epigenetic inactivation of hMLH1 was an early event in the malignant transformation of ovarian EMs. Epigenetic inactivation of hMLH1 in eutopic endometria was synchronous with that in ectopic endometria and the epigenetic inactivation of hMLH1 in eutopic endometria of EMs might be a potential molecular tool for early diagnosis of the malignant transformation of ovarian EMs.

Bioessays. 2012 Jan;34(1):26-35. doi: 10.1002/bies.201100099. Epub 2011 Nov 7.

The evolution of menstruation: a new model for genetic assimilation: explaining molecular origins of maternal responses to fetal invasiveness.

Emera D, Romero R, Wagner G.

Source

Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Abstract

Why do humans menstruate while most mammals do not? Here, we present our answer to this long-debated question, arguing that (i) menstruation occurs as a mechanistic consequence of hormone-induced differentiation of the endometrium (referred to as spontaneous decidualization, or SD); (ii) SD evolved because of maternal-fetal conflict; and (iii) SD evolved by genetic assimilation of the decidualization reaction, which is induced by the fetus in non-menstruating species. The idea that menstruation occurs as a consequence of SD has been proposed in the past, but here we present a novel hypothesis on how SD evolved. We argue that decidualization became genetically stabilized in menstruating lineages, allowing females to prepare for pregnancy without any signal from the fetus. We present three models for the evolution of SD by genetic assimilation, based on recent advances in our understanding of the mechanisms of endometrial differentiation and implantation. Testing these models will ultimately shed light on the evolutionary significance of menstruation, as well as on the etiology of human reproductive disorders like endometriosis and recurrent pregnancy loss.

Comment in

Biofizika. 2012 Jan-Feb;57(1):105-9.

The dinitrosyl-iron complexes with cysteine block the development of experimental endometriosis in rats.

[Article in Russian]

Burgova EN, Tkachev NA, Vanin AF.

Abstract

It has been shown that the administration of 0,5 ml of 5 mM aqueous solution of dinitrosyl-iron complexes (DNIC) with cysteine alleviated the development of experimental endometriosis in rats induced by surgical way: the size of endometriomes decreased 1.85 times when the DNIC was added every day during 10 days. The effect was suggested to be due to cytotoxic action of NO molecules and nitrosonium ions (NO+) released from rapidly decomposed DNIC in animal organism on endometriome tissues.

Biomaterials. 2012 Jan;33(2):634-43. Epub 2011 Oct 13.

Gene therapy of endometriosis introduced by polymeric micelles with glycolipid-like structure.

Zhao MD, Sun YM, Fu GF, Du YZ, Chen FY, Yuan H, Zheng CH, Zhang XM, Hu FQ.

Source

Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, PR China.

Abstract

To reduce the side effects and improve the lack of clinical treatment countermeasures in endometriosis chemotherapy, a polymeric micelle gene delivery system composed of lipid grafted chitosan micelles (CSO-SA) and the pigment epithelium derived factor (PEDF) was designed. Due to the cationic property, the glycolipid-like micelles could compact the PEDF to form complexes nanoparticles. The complexes nanoparticles with an N/P at 9.6 had 135.6 nm volume average hydrodynamic diameters with a narrow size distribution, and 6.4 ± 0.1 mV surface potential. PEDF can be distributed to endometriotic lesions in a rat model of peritoneal endometriosis mediated by CSO-SA via the intravenous injection. It showed that the CSO-SA/PEDF nanoparticles gene therapy caused decrease in the sizes of the endometriotic lesions and atrophy and degeneration of ectopic endometrium significantly. And it showed no toxicity to the reproductive organs under electron microscope observation. In addition, a reduction in microvessel density labeled by Von Willebrand factor was observed and no decrease in α-Smooth Muscle Actine-positive mature vessels. And the index of apoptotic was increased significantly in endometriotic lesions of CSO-SA/PEDF group. So, glycolipid-like structure micelles mediated PEDF gene delivery system could be used as an effective treatment approach for endometriosis disease.

Biostatistics. 2012 Jan;13(1):74-88. Epub 2011 Sep 10.

Latent class models for joint analysis of disease prevalence and high-dimensional semicontinuous biomarker data.

Zhang B, Chen Z, Albert PS.

Source

Biostatistics and Bioinformatics Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. bo.zhang@nih.gov

Abstract

High-dimensional biomarker data are often collected in epidemiological studies when assessing the association between biomarkers and human disease is of interest. We develop a latent class modeling approach for joint analysis of high-dimensional semicontinuous biomarker data and a binary disease outcome. To model the relationship between complex biomarker expression patterns and disease risk, we use latent risk classes to link the 2 modeling components. We characterize complex biomarker-specific differences through biomarker-specific random effects, so that different biomarkers can have different baseline (low-risk) values as well as different between-class differences. The proposed approach also accommodates data features that are common in environmental toxicology and other biomarker exposure data, including a large number of biomarkers, numerous zero values, and complex mean-variance relationship in the biomarkers levels. A Monte Carlo EM (MCEM) algorithm is proposed for parameter estimation. Both the MCEM algorithm and model selection procedures are shown to work well in simulations and applications. In applying the proposed approach to an epidemiological study that examined the relationship between environmental polychlorinated biphenyl (PCB) exposure and the risk of endometriosis, we identified a highly significant overall effect of PCB concentrations on the risk of endometriosis.

Brain Behav Immun. 2012 Jan;26(1):132-41. Epub 2011 Aug 25.

Imbalance between sympathetic and sensory innervation in peritoneal endometriosis.

Arnold J, Barcena de Arellano ML, Rüster C, Vercellino GF, Chiantera V, Schneider A, Mechsner S.

Source

Endometriosis Research Centre Charité, Department of Gynaecology, Charité, Campus Benjamin Franklin, Berlin, Germany.

Abstract

To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy peritoneum (n=12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleukin (IL)-1β expression was correlate with the nerve fibre density. Peritoneal fluids from patients with endometriosis (n=40) and without endometriosis (n=20) were used for the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG) and sympathetic ganglia were stained with anti-growth associated protein 43 (anti-GAP 43), anti-SP and anti-TH. We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain.

Chin Med J (Engl). 2012 Jan;125(2):209-13.

Anatomical distribution of pelvic deep infiltrating endometriosis and its relationship with pain symptoms.

Dai Y, Leng JH, Lang JH, Li XY, Zhang JJ.

Source

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing 100730, China.

Abstract

BACKGROUND:

Endometriosis is a controversial and enigmatic disease. Deep infiltrating endometriosis (DIE) is responsible for painful symptoms and is the least understood type of endometriosis. Little work has been devoted to define the location of DIE lesions and its relationships with pain. The aim of the study was to investigate the relationship between the anatomical distribution of DIE lesions and pain symptoms.

METHODS:

Clinical data from 354 patients between May 2003 and December 2007 with laparoscopically diagnosed endometriosis were collected including 177 DIE patients and 177 non-DIE patients. The pain symptoms, including dysmenorrhea (DM), chronic pelvic pain (CPP, defined as intermittent or permanent pelvic pain, not related to the menstruation and longer than 6 months), deep dyspareunia (pelvic pain at intercourse) and dyschezia (pelvic pain with defecation), were recorded for every patient before operation. Endometriotic lesions were recorded by their anatomical distributions, the depth of infiltration and lesion colors. And the relationship between the anatomical distribution of DIE lesions and pain symptoms was analyzed. Pearson’s chi-square test or Fisher’s exact test, one-way analysis of variance (ANOVA) and linear regression and binary Logistic regression were used for statistical analysis.

RESULTS:

The duration ((13.79 ± 3.94) years) of pain suffering in DIE patients was much longer than that of non-DIE patients (P < 0.01). In DIE patients, 60.7% of the uterosacral ligament (USL) nodules were bilateral (P < 0.01); 44.6% of the cul-de-sacs were completely blocked. Rectum invasion was observed in 19.9% of DIE patients (P = 0.03); pelvic adhesion was also more common. Up to 98.41% of the deep infiltrative lesions were located in the posterior pelvic compartment. DIE lesions were also found in bladder (1.58%), USL (67.08%), cul-de-sac (12.02%), recto-vaginal septum (12.66%), rectum and rectosigmoid junction (2.85%) and ureter (3.80%). The odds ratio of USL-DIE for CPP, deep dyspareunia, dyschezia were 2.52, 1.29 and 2.24 respectively. And the depth of infiltration correlated with the severity of dysmenorrhea.

CONCLUSIONS:

DIE lesions were associated with severe pain symptoms. The main distribution of DIE lesions was in the posterior pelvic compartment, and was more widespread and severe in DIE patients. Moreover, resection of these DIE lesions are very important to treat the pain symptoms.

Clin Dev Immunol. 2012;2012:606459. Epub 2011 Oct 5.

Follicular proinflammatory cytokines and chemokines as markers of IVF success.

Sarapik A, Velthut A, Haller-Kikkatalo K, Faure GC, Béné MC, de Carvalho Bittencourt M, Massin F, Uibo R, Salumets A.

Source

Department of Immunology, Institute of General and Molecular Pathology, University of Tartu, Ravila 19, Tartu 50411, Estonia.

Abstract

Cytokines are key modulators of the immune system and also contribute to regulation of the ovarian cycle. In this study, Bender MedSystems FlowCytomix technology was used to analyze follicular cytokines (proinflammatory: IL-1β, IL-6, IL-18, IFN-γ, IFN-α, TNF-α, IL-12, and IL-23;, and anti-inflammatory: G-CSF), chemokines (MIP-1α, MIP-1β, MCP-1, RANTES, and IL-8), and other biomarkers (sAPO-1/Fas, CD44(v6)) in 153 women undergoing in vitro fertilization (IVF). Cytokine origin was studied by mRNA analysis of granulosa cells. Higher follicular MIP-1α and CD44(v6) were found to correlate with polycystic ovary syndrome, IL-23, INF-γ, and TNF-α with endometriosis, higher CD44(v6) but lower IL-β and INF-α correlated with tubal factor infertility, and lower levels of IL-18 and CD44(v6) characterized unexplained infertility. IL-12 positively correlated with oocyte fertilization and embryo development, while increased IL-18, IL-8, and MIP-1β were associated with successful IVF-induced pregnancy.

Clin Exp Obstet Gynecol. 2012;39(1):107-11.

Effect of fibrin glue and comparison with suture on experimental induction of endometriosis in a rat endometrial autograft model.

Boztosun A, Ozer H, Atilgan R, Açmaz G, Yalta T, Müderris II, Yanik A.

Source

Department of Obstetrics and Gynecology, Cumhuriyet University, Sivas, Turkey. abdullahboztosunyrd@hotmail.com

Abstract

OBJECTIVE:

The effects of fibrin glue (FG) and suture were investigated and compared with experimental induction in an endometriosis model.

MATERIAL AND METHODS:

A randomized, controlled, and double-blind study was performed with 25 adult female Wistar Albino rats. Two autologous endometrial grafts were obtained from each of the rats. The endometrial grafts were transplanted by gluing with FG on the right abdominal wall and suturing with only 5/0 prolene on the left in ten rats. Gluing+suturing and after suturing over the covering with FG of the endometrial graft were performed, respectively, on the right and left in another ten rats. Covering with FG glue of the endometrial graft was performed in another five rats. The endometriosis-like lesions and intraperitoneal adhesions were evaluated macroscopically and histopathologically.

RESULTS:

The mean volume (31.4 +/- 17.3), adhesion (0.8 +/- 0.7) and inflammatory reaction (1.2 +/- 0.7) score of the implants in the group using only FG were significantly lower than in the group using suture [respectively, (49.2 +/- 20.6), (2.4 +/- 0.8), (2.2 +/- 0.8)] (p < 0.05).

CONCLUSIONS:

Our results demonstrate the general feasibility of reproducible and reliable endometrial graft fixation with FG onto the inner abdominal surface in rats. Furthermore, several advantageous characteristics could be demonstrated such as less inflammation and fewer adhesions.

Clin Med Insights Case Rep. 2012;5:63-68. Epub 2012 May 21.

Leiomyomatosis Peritonealis Disseminata Associated with Endometriosis and Multiple Uterus-Like Mass: Report of Two Cases.

Carvalho FM, Carvalho JP, Pereira RM, Ceccato BP Junior, Lacordia R, Baracat EC.

Source

Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo (SP), Brazil.

Abstract

Leiomyomatosis peritonealis disseminate (LPD) is a rare benign disease of unknown etiology of women in reproductive age. A few reported cases of association with endometriosis have been described suggesting a possible origin from submesothelial multipotential cells. We present two cases of LPD associated with endometriosis expressing smooth muscle metaplasia, and some of the nodules with aspects of uterus-like mass. Laparoscopy, gross findings, and the pathological and immunohistochemical study of the surgical specimens were described. Our findings suggest an endometriotic origin for the LPD and indicate that the therapeutic approach might contemplate the surgical reduction of the nodules and endometriosis treatment.

Clinics (Sao Paulo). 2012;67(5):437-41.

A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses.

Anton C, Carvalho FM, Oliveira EI, Maciel GA, Baracat EC, Carvalho JP.

Source

Faculdade de Medicina, Unversidade de São Paulo, São Paulo, SP, Brazil.

Abstract

OBJECTIVE:

Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combination to evaluate their utility for establishing this type of patient referral system.

METHODS:

Patients who had been diagnosed with ovarian masses through imaging analyses (n = 128) were assessed for their expression of the tumor markers CA125 and HE4. The ROMA and RMI values were also determined. The sensitivity and specificity of each parameter were calculated using receiver operating characteristic curves according to the area under the curve (AUC) for each method.

RESULTS:

The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4%, 79.6%, 74.1%, and 63%, respectively. Among carcinomas, the sensitivities of CA125, HE4, ROMA (pre-and post-menopausal), and RMI were 93.5%, 87.1%, 80%, 95.2%, and 87.1%, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent.

CONCLUSION:

There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy potential were considered low-risk, which may be used as an acceptable assessment method for referring patients to reference centers.

Curr Med Chem. 2012;19(15):2406-13.

Role of microRNAs in gynecological pathology.

Gilabert-Estelles J, Braza-Boils A, Ramon LA, Zorio E, Medina P, Espana F, Estelles A.

Source

Gynecology Service, Hospital Universitario Dr Peset, Valencia, Spain. estelles_amp@gva.es

Abstract

microRNAs (miRNAs) are 21-22 nucleotide non-coding RNAs that regulate gene expression and play fundamental roles in biological processes. These small molecules bind to target mRNAs, leading to translational repression and/or mRNA degradation. Aberrant miRNA expression is associated with several human diseases such as cancer, cardiovascular disorders, inflammatory diseases and gynecological pathology. The present article reviews the role of miRNAs in four gynecological disorders that affect the ovary or the uterus, one benign and frequent disease (endometriosis) that is classified as a tumor-like lesion and three malignant gynecological diseases (endometrial, cervical and ovarian cancers). Endometriosis, defined as the presence of endometrium outside the uterus, is one of the most frequent benign gynecological diseases. Similarly to tumor metastasis, endometriotic implants require neovascularization to proliferate, invade the extracellular matrix and establish an endometriotic lesion. Despite its high prevalence and incapacitating symptoms, the exact pathogenic mechanism of endometriosis remains unsolved. A relationship between endometriosis and gynecological cancer, especially ovarian cancer, has been reported. Endometriosis is a multifactorial and polygenic disease, and emerging data provide evidence that a dysregulation of miRNA expression may be involved. miRNAs appear to be potent regulators of gene expression in endometriosis, raising the prospect of using miRNAs as biomarkers and therapeutic tools in this disease. In cancer, miRNAs have an important role as regulatory molecules, acting as oncogenes (oncomiRs) or tumor suppressors. Endometrial cancer is one of the most frequent gynecological malignancies in the developed countries. Cervical cancer, also one of the most common cancers in women, is associated with high-risk human papillomaviruses although this infection alone may not be enough to induce the malignant transformation. Ovarian cancer is the fifth leading cause of all cancer-related deaths among women. Over 80% of cases are diagnosed at an advanced stage, with a reduced five-year survival rate. Recent studies have shown that miRNAs are aberrantly expressed in different human cancer types, including endometrial, cervical and ovarian cancer, and that specific dysregulated miRNAs may act as biomarkers of patients’ outcome. Recently, miRNAs have been detected in serum and plasma, and circulating miRNA expression profiles have now been associated with a range of different tumor types. Their accessibility in peripheral blood and stability given the fact that miRNAs circulate confined within exosomes, make researchers foster hope in their role as emerging biomarkers of cancer and other disorders. The development of therapies that might block the expression or mimic the functions of miRNAs could represent new therapeutic strategies for any of the aforementioned gynecological disorders.

Duodecim. 2012;128(8):851-7.

Infertility and risk of cancer.

[Article in Finnish]

Hippeläinen M.

Source

KYS, naistentautien klinikka.

Abstract

Ovulation problems, ovarian endometriosis and impaired sperm quality may be factors underlying infertility and possibly predisposing to cancer diseases. Infertility therapies utilize products that alter the hormonal balance and may in theory increase the risk of cancer. Handling of gametes in the laboratory is also likely to influence gene regulation. Ovulation induction therapies may increase the risk of uterine cancer, and in vitro fertilization (IVF) therapies may increase ovarian tumors. Children born after IVF therapies seem to have a statistically elevated risk of cancer. Instead of risk ratios, the use of clear figures is recommended in patient information.

Eur J Gynaecol Oncol. 2012;33(2):230-2.

Borderline clear cell adenofibroma of the ovary associated with ovarian endometriosis: a case report.

Vasilakaki T, Skafida E, Arkoumani E, Grammatoglou X, Firfiris N, Manoloudaki K.

Source

Department of Pathology, Tzaneion General Hospital of Piraeus, Greece. thvasilakaki@yahoo.gr

Abstract

Clear cell tumours of the ovary are relatively uncommon. Most of them are clear cell carcinomas. Benign and borderline clear cell tumours are extremely rare and almost always fibromatous. We report a case of a 34-year-old woman. Ultrasound and computed tomography showed a right ovarian mass 8 cm in diameter. The patient underwent right salpingo-oophorectomy. Microscopic examination revealed glands and cysts different in size and shape within an abundant stromal component without evidence of stromal invasion. Many cysts and glands were lined by a single layer of flattened, cuboidal or hobnail cells with mild to moderate cytologic atypia and prominent nucleoli. Psammomatous calcifications were occasionally indentified. Features of endometriosis were also present adjacent to the tumour. Lesional cells were positive for Ker 7 and CA125. Staining for p53 was focally positive. Based on the above characteristic morphologic and immunohistochemical findings a diagnosis of borderline clear cell adenofibroma was made. The patient was free of recurrence four years after surgery.

Eur J Obstet Gynecol Reprod Biol. 2012 Jan;160(1):35-9. Epub 2011 Nov 17.

The effect of the hormonal milieu of pregnancy on deep infiltrating endometriosis: serial ultrasound assessment of changes in size and pattern of deep endometriotic lesions.

Coccia ME, Rizzello F, Palagiano A, Scarselli G.

Source

Department of Science for the Woman and Child’s Health, University of Florence, via Ippolito Nievo, 2, 50100 Florence, Italy. cocciame@tin.it

Abstract

BACKGROUND:

Deep infiltrating endometriosis (DIE) is associated with severe painful symptoms and represents a complex management challenge.

OBJECTIVE:

To analyse the effect of pregnancy on deep infiltrating lesions and related symptomatology.

STUDY DESIGN:

As part of a longitudinal study performed over the past 3 years to determine the efficacy of hormonal treatment in treating women with DIE, we identified three cases of advanced pelvic endometriosis, all with DIE (deep recto-vaginal and recto-sigmoid involvement) where patients achieved spontaneous pregnancies. They were followed up by transvaginal ultrasound (TV-US). The main outcome measures were analysis of the size and echographic pattern of deep infiltrating lesions of endometriosis and evaluation of clinical symptoms during pregnancy.

RESULTS:

We observed modifications in lesion size and pattern. In the two patients observed in the third trimester, the lesions were more homogeneous with less evident limits of nodules and band-like echoes, less fibrotic-like. All patients showed complete resolution of symptoms during pregnancy.

CONCLUSIONS:

The hormonal environment produced by pregnancy might determine significant modifications of endometriotic lesions and reduce painful symptoms. As surgery for DIE is difficult, complex and can lead to major complications, the achievement of a pregnancy-specific hormonal state, through pregnancy or hormonal treatment, may be a valid option in selected cases.

Eur J Obstet Gynecol Reprod Biol. 2012 Jan;160(1):74-8. Epub 2011 Nov 5.

Differential expression of MMP-2, MMP-9 and PCNA in endometriosis and endometrial carcinoma.

Weigel MT, Krämer J, Schem C, Wenners A, Alkatout I, Jonat W, Maass N, Mundhenke C.

Source

Department of Obstetrics and Gynecology, Kiel University, Arnold-Heller-Str. 3, 24105 Kiel, Germany.

Abstract

OBJECTIVES:

Endometriosis is a common gynaecological disease with clinical symptoms such as chronic pain, infertility and intra-abdominal adhesions. Different theories on the pathogenesis of endometriosis and especially its aggressive subtype with infiltrative growth have been discussed. The objective of this study is to evaluate differences in proliferation and invasive properties of invasive colorectal endometriosis, superficial peritoneal endometriosis and endometrial carcinoma (G1 and G2).

STUDY DESIGN:

Paraffin embedded tissues of peritoneal endometriosis, endometriosis of the intestine and endometrial carcinoma from 97 patients were stained immunohistochemically to assess differences in expression patterns of matrix metalloproteinases (MMP-2, MMP-9) as markers of invasion and the marker of proliferation PCNA. MMP expression was evaluated using the Immuno Reactive Score (IRS) (combining positive cell ratio and staining intensity) and PCNA expression was assessed as the percentage of positively stained cells in representative areas.

RESULTS:

MMP-2, MMP-9 and PCNA showed differential expression patterns in the different tissues examined. MMP-2 and PCNA expression was stronger in invasive colorectal endometriosis than in superficial peritoneal endometriosis (p=0.0394). MMP-9, however, was more frequently expressed in peritoneal endometriosis (59.1%) than in colorectal endometriosis (44.4%). This result did not reach statistical significance. When colorectal endometriosis was compared to low grade endometrial carcinoma, proliferation detected by PCNA was significantly higher in endometriosis (p=0.0008). MMP-2 and MMP-9 showed higher expression in endometrial carcinoma than in endometriosis.

CONCLUSIONS:

There are obvious differences in expression patterns of MMP-2, MMP-9 and PCNA in different stages of endometriosis and in endometrial cancer. These markers can be helpful to evaluate aggressiveness and invasiveness of endometriosis in different localizations. The results obtained could be of relevance for a better understanding of the pathogenesis of endometriosis and the development of an individual therapy concept.

Eur J Obstet Gynecol Reprod Biol. 2012 Jan;160(1):79-83. Epub 2011 Nov 1.

Prevalence and incidence of diagnosed endometriosis and risk of endometriosis in patients with endometriosis-related symptoms: findings from a statutory health insurance-based cohort in Germany.

Abbas S, Ihle P, Köster I, Schubert I.

Source

PMV Research Group at Department of Child and Adolescent Psychiatry and Psychotherapy, University of Cologne, Herderstr. 52, 50931 Cologne, Germany. sascha.abbas@uk-koeln.de

Abstract

OBJECTIVE:

The objectives were: (a) to determine the administrative prevalence and incidence of endometriosis and (b) to assess the risk of endometriosis associated with endometriosis-related symptoms.

STUDY DESIGN:

The study is based on inpatient and outpatient data from a statutory health insurance fund in Germany. For prevalence and incidence definition 62,323 women aged 15-54 continuously insured in 2007 were identified. The prevalence and incidence of endometriosis in 2007 were calculated standardized to the age distribution in Germany. In a further prospective cohort study based within the health insurance sample 2095 patients with endometriosis-related symptoms and 8380 age-matched asymptomatic controls were identified. Endometriosis follow-up was from 2004 to 2008. Cox proportional hazard regression was used to examine the risk of endometriosis associated with endometriosis-related symptoms, such as pelvic pain, dysmenorrhoea, dyspareunia, menorrhagia, post-coital bleeding, inter-menstrual pain and ovarian cysts. Relative risks (RR) and 95% confidence intervals (CI) were calculated.

RESULTS:

Standardized prevalence and incidence rates were 8.1 and 3.5 per 1000 women, respectively. The highest prevalence was observed in women aged 35-44 with 12.8 per 1000 women. Median follow-up was 4.5 years. Risk of endometriosis associated with endometriosis-related symptomatology was RR (95% CI)=4.95 (3.67-6.68); 4.5% of all symptomatic women were diagnosed with endometriosis in a median follow-up of 4.5 years. The highest risk was observed in women aged 35-44 [RR (95% CI)=6.29 (4.00-9.90)] with 7.6% of all symptomatic women receiving a diagnosis of endometriosis during the follow-up.

CONCLUSION:

Prevalence estimates based on population-based administrative data were lower than described in the literature. Risk of endometriosis was increased in women with endometriosis-related symptoms. However, those symptoms were of limited predictive value for endometriosis as only a small proportion of symptomatic patients were diagnosed with endometriosis in the follow-up.

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

Endocrine disruptors in utero cause ovarian damages linked to endometriosis.

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

Source

Fondazione Italiana Endometriosi, Rome, Italy. research@endometriosi.it

Abstract

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

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

Fertility preservation in women with ovarian endometriosis.

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

Source

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

Abstract

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

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

Proteinase-activated receptors in the endometrium and endometriosis.

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

Source

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan. yutakaos-tky@umin.ac.jp

Abstract

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

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