Pag. 12

J Obstet Gynaecol Res.2012 Apr 30. doi: 10.1111/j.1447-0756.2012.01845.x. [Epub ahead of print]

Histological assessment of impact of ovarian endometrioma and laparoscopic cystectomy on ovarian reserve.

Kuroda M, Kuroda K, Arakawa A, Fukumura Y, Kitade M, Kikuchi I, Kumakiri J, Matsuoka S, Brosens IA, Brosens JJ, Takeda S, Yao T.

Source

Departments of Human Pathology Obstetrics and Gynaecology, Juntendo University Faculty of Medicine, Tokyo, Japan Leuven Institute of Fertility and Embryology, Leuven, Belgium Clinical Sciences Research Institute, University of Warwick, Coventry, UK.

Abstract

Aim: The rate of oocyte decline follows a biphasic pattern, characterized by acceleration between 32 and 38years old. Ovarian reserve is also affected by external factors, including ovarian disease and iatrogenic damage. The aim of this study was to histologically evaluate the impact of ovarian endometriomas, laparoscopic cystectomy, and age on follicle reserve in healthy ovarian tissues and in surgically resected cyst walls. Material and Methods: Sixty-one patients were found to have ovarian endometriomas and 42 patients non-endometriotic cysts. A small amount of normal ovarian tissue was obtained during ovarian cystectomy. The follicles in normal ovarian tissue and resected cyst walls were histologically evaluated. Results: The density of follicles in ovarian tissues correlated with the age of the patients in both groups. In women aged <35years, the relative density of follicles in healthy ovarian tissues was consistently lower in the endometriotic cyst group compared to the non-endometriotic cyst group, with the relative ratio at age 20, 30 and 35years calculated to be 35.4%, 46.8% and 62.7%, respectively. There was no significant difference between the groups in patients over the age of 35. The resection rate of normal ovarian tissue in cystectomy specimen of the endometriosis group was significantly higher than in the non-endometriotic cyst group (P<0.001). Conclusions: Our data suggest that ovarian endometriomas have a detrimental impact on follicle reserve in younger patients. Further, laparoscopic cystectomy for endometriomas may accelerate the rate of oocyte loss associated with aging.

World J Radiol.2012 Apr 28;4(4):135-40.

Reliable clinical and sonographic findings in the diagnosis of abdominal wall endometriosis near cesarean section scar.

Francica G.

Source

Giampiero Francica, Unit of Diagnostic and Interventional ultrasound, Camilliani Hospital, “S. Maria della Pieta”, S. Rocco St. 9, 80026 Casoria, Italy.

Abstract

AIM:

To highlight sonographic and clinical characteristics of scar endometrioma with special emphasis on size-related features.

METHODS:

Thirty women (mean age 30.6 years, range 20-42 years) with 33 scar endometriomas (mean diameter 27.1 mm, range 7-60 mm) were consecutively studied by Sonography and Color Doppler examination prior to surgery. Pathological examination was available in all cases.

RESULTS:

The most frequent (24 of 33 nodules, 74%) sonographic B-mode aspect of endometrioma was that of an inhomogenously hypoechoic roundish nodule with fibrotic changes (in the form of hyperechoic spots or strands), a peripheral inflammatory hyperechoic ring, spiculated margins and a single vascular pedicle entering the mass at the periphery. On average, 1.6 cesarean sections were recorded per patient (range 1-3). The median interval between the last cesarean section and admission to hospital was 36 mo (range 12-120 mo) and the median duration of symptoms before admission was 25.7 mo (range 0.5-80 mo). 13 patients had 13 large endometriomas (≥ 30 mm) with a mean lesion diameter of 41.3 ± 9.02 mm (range 30-60 mm). Seventeen women had 20 small endometriomas with a mean lesion size of 18.2 ± 5.17 mm (range 7-26 mm). The mean interval between the last cesarean section and admission to hospital (66.0 mo vs 39.6 mo, P < 0.01) and the mean duration of symptoms before admission (43.0 mo vs 17.4 mo, P < 0.01) were significantly longer in patients with large endometriomas; in addition, a statistically significant higher percentage of patients with large implants had undergone previous inconclusive diagnostic examinations, including either computed tomography/magnetic resonance imaging/fine needle biopsy/laparoscopy (38.4% vs 0%, P < 0.05). On sonography, large endometriomas showed frequent cystic portions and fistulous tracts (P < 0.02), loss of round/oval shape (P < 0.04) along with increased vascularity (P < 0.04).

CONCLUSION:

Endometrioma near cesarean section scar is an often neglected disease, but knowledge of its clinical and sonographic findings may prevent a delay in diagnosis that typically occurs in patients with larger (≥ 3 cm) endometriomas.

Andrologia.2012 Apr 27. doi: 10.1111/j.1439-0272.2012.01295.x. [Epub ahead of print]

Comparing the effectiveness of infertility treatments by numbers needed to treat (NNT).

Comhaire F, Decleer W.

Source

Brakelmeersstraat, Sint Martens-Latem, Belgium.

Abstract

To compare the clinical efficiency of different modes of treatment of infertile couples and to estimate the possible benefit of nutraceutical food supplementation (NFS), the numbers needed to treat (NNT) was calculated in 4143 infertile couples based on controlled trials in recent literature and personal data. The NNT expresses the number of individuals who need to be treated to obtain one complementary pregnancy. In female infertility, the NNT of mild or moderate endometriosis was 8.4, and in anti-estrogens treatment of anovulation, it was 5.9. In tamoxifen treatment of idiopathic oligozoospermia, NNT was 3.9, and in antioxidant supplementation, it was 7.8. Treatment of varicocele yielded NNT of 6.3 and 6.8 after 1 year in multi- or single-centre trials, respectively, and NFS lowered the NNT after 3 months to 2.6. Adding NFS to the male partner increased the ongoing pregnancy rate by IVF with NNT of 8.3, and adding NFS to both partners reduced the NNT to 4.0. Although these results were obtained in heterogeneous trials and populations, it is suggested that the NNT should be useful for comparing the effectiveness of different modes of treatment of the infertile couple, and that complementary nutraceutical food supplementation may be beneficial.

Emerg Radiol.2012 Apr 27. [Epub ahead of print]

Nongynecological endometriosis presenting as an acute abdomen.

Hwang BJ, Jafferjee N, Paniz-Mondolfi A, Baer J, Cooke K, Frager D.

Source

Department of Radiology, St. Luke’s-Roosevelt Hospital, Columbia University College of Physicians, 1000 Tenth Avenue, New York, NY, 10019, USA, behwang@chpnet.org.

Abstract

Endometriosis is a highly prevalent disease that affects up to 10 % of menstruating women. Patients commonly present with pelvic pain or infertility, although the range of clinical symptoms varies widely. Affected women may be asymptomatic or experience mild, moderate, or severe pain that fluctuates with hormonal cycles. Patients who suffer extreme pain may seek immediate care and present to the emergency department with clinical signs of an acute abdomen. In the case of patients without a prior history of endometriosis, the differential diagnosis is broad and making the correct clinical and radiologic diagnosis in the emergency setting can be challenging. In some cases, the diagnosis is only made after surgical or histopathological analysis. Prompt and accurate clinical and radiological evaluation is necessary because complications of endometriosis, such as bowel obstruction and appendicitis, may require immediate surgical intervention. This pictorial essay analyzes nongynecological manifestations of endometriosis that may have a clinical presentation of an acute abdominal emergency. Atypical clinical presentations and unusual sites and complications of endometriosis are discussed, as well as the differential diagnostic considerations. The radiologic features of endometriosis are shown on multiple modalities, including computed tomography, magnetic resonance imaging, and ultrasound.

Reprod Biol Endocrinol.2012 Apr 27;10(1):34. [Epub ahead of print]

Expression of the T regulatory cell transcription factor FoxP3 in peri-implantation phase endometrium in infertile women with endometriosis.

Chen S, Zhang J, Huang C, Lu W, Liang Y, Wan X.

Abstract

ABSTRACT:

BACKGROUND:

Endometriosis (EM) is highly associated with infertility. The precise mechanism underlying EM-associated infertility remains controversial. This study aimed to investigate the pathogenesis of infertility in women with EM by comparing FoxP3+ T regulatory cells (Tregs) expression in the eutopic endometrium of infertile women with EM and endometrium from healthy fertile women.

METHODS:

As a marker of Tregs, FoxP3 expression was analyzed in eutopic endometrium during the peri-implantation phase in infertile women with mild EM (n = 7), advanced EM (n = 20), and normally fertile women without EM (n = 20). FoxP3 mRNA expression was analyzed by quantitative real-time RT-PCR. FoxP3 protein expression was assessed by immunohistochemistry.

RESULTS:

FoxP3 mRNA expression in all infertile patients with EM was significantly higher than the control group (P<0.05) by non-parametric Mann-Whitney U-test. Further analysis based on the extent of EM revealed that FoxP3 mRNA expression in infertile patients with advanced EM was significantly higher than the mild EM group and the control group (P<0.05). Immunohistochemistry analysis showed predominant positive staining for FoxP3 protein in the endometrial stroma. In addition, the number of FoxP3+ cells in the eutopic endometrium of infertile women with advanced EM was marginally higher than the mild EM group and the control group, although the differences were not statistically significant (P>0.05) by two-tailed t-tests.

CONCLUSIONS:

These findings suggest that FoxP3+ Tregs in the peri-implantation endometrium might participate in the pathogenesis of advanced EM. However, they are not directly involved in the pathogenesis of advanced EM associated with infertility. The differential expression of FoxP3 in infertile women with mild EM and advanced EM implicates that notable differences in the uterine immune status are likely involved in the pathogenesis of mild EM associated with infertility in the peri-implantation endometrium.

Am J Reprod Immunol.2012 Apr 26. doi: 10.1111/j.1600-0897.2012.01147.x. [Epub ahead of print]

Imbalance in Cytokines from Interleukin-1 Family – Role in Pathogenesis of Endometriosis.

Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z.

Source

Department of Immunology and Serology, Medical University of Silesia, Katowice, Poland.

Abstract

PROBLEM:

To assess whether interleukin (IL)-1beta, IL-18 and interleukin-1 converting enzyme (ICE) are involved in the pathogenesis of endometriosis.

METHOD OF STUDY:

Peritoneal fluid (PF) was obtained from 85 women with and without endometriosis. Peritoneal macrophages were cultured and the culture media collected. IL-1beta, IL-18 and ICE levels were measured by the enzyme-linked immunosorbent assay (ELISA).

RESULTS:

Levels of IL-1beta and ICE in PF of women with endometriosis were higher than those in the control group. However, PF level of IL-18 was significantly lower in the study group than in the controls. Higher secretion of IL-1beta by peritoneal macrophages and lower IL-18 and ICE in endometriosis patients than in control were observed. Following lipopolysaccharide (LPS) stimulation, the macrophages secreted more IL-1beta, IL-18 and ICE in all groups.

CONCLUSIONS:

The results pointed to impairment of the secretion of the IL-1 cytokine family in endometriosis. Invalid IL-1beta and IL-18 maturation by ICE may be an important pathogenic factor in endometriosis.

Reprod Sci.2012 Apr 26. [Epub ahead of print]

High Lymph Vessel Density and Expression of Lymphatic Growth Factors in Peritoneal Endometriosis.

Reichelt U, Keichel S, Barcena de Arellano ML, Chiantera V, Schneider A, Mechsner S.

Abstract

To investigate the occurrence of lymph vessels and lymphangiogenic growth factors in peritoneal lesions, we performed immunohistochemical staining of peritoneal lesions of 37 patients with antibodies against podoplanin (D2-40), lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), prospero homeobox protein 1 (Prox-1), vascular epithelial growth factor (VEGF)-C/VEGF-D. Overall, 10 lesions were double stained against D2-40 and von Willebrand factor. The lymph vessel density in peritoneal lesion was significantly higher in comparison with healthy peritoneum. All lymph vessel makers could be detected, whereby the lymph vessel density of LYVE-1- and Prox-1-positive lymph vessels was significantly higher than the lymph vessel density of D2-40-positive lymph vessels. Endometriotic epithelial cells and stromal cells (SCs) showed a moderate-to-strong VEGF-C/VEGF-D expression. The VEGF-C-/VEGF-D-positive macrophages in endometriotic SCs could be observed. The lymphatic vasculature seems to form a further component of peritoneal lesions and could be involved in the inflammatory process. These data demonstrated a further step in the clarification of the pathogenesis of endometriosis.

Ultrasound Obstet Gynecol.2012 Apr 25. doi: 10.1002/uog.11179. [Epub ahead of print]

Accuracy of transvaginal sonography and contrast-enhanced MR-colonography for the pre-surgical staging of deep infiltrating endometriosis.

Vimercati A, Achilarre MT, Scardapane A, Lorusso F, Ceci O, Mangiatordi G, Angelelli G, Van Herendael B, Selvaggi L, Bettocchi S.

Source

Department of Gynecology Obstetrics and Neonatology (DiGON), I Operative Unit of Obstetrics and Gynecology, University of Bari, Bari, Italy.

Abstract

Objectives: The aim of this study was to investigate the accuracy of transvaginal sonography (TVS) and contrast-enhanced magnetic resonance-colonography (CE-MR-C) for the pre-surgical assessment of deep infiltrating endometriosis (DIE). Methods Ninety women were prospectively enrolled for a suspicion of DIE. All patients underwent a TVS and a CE-MR-C performed blindly, before laparoscopy. The sites of DIE examined by both imaging techniques were: recto-vaginal septum, pouch of Douglas, utero-sacral ligaments, vesico-uterine pouch, bowel, bladder and vagina. The presence of adhesions, the involvement of adnexa and of a previous abdominal scar, in case of a clinical suspicion, were also evaluated. TVS and CE-MR-C findings were compared with laparoscopic and histological results. Results Endometriosis was confirmed by laparoscopy in 95.6% of cases (86//90). In 82.2% (74/90) of patients there was DIE. The global accuracy, sensitivity, specificity, positive predictive values, negative predictive values, positive likelihood ratios and negative likelihood ratios were 89.2%, 81.1%, 94.2%, 89.6%, 89.0%, 13.9 and 0.2 for TVS, 87.2%, 71.1%, 97.1%, 93.7%, 84.6%, 24.4 and 0.3 for CE-MR-C. CE-MR-C allowed to diagnose all cases of bowel involvement; the accuracy for infiltration and stenosis was 100%. The accuracy of TVS for recto-sigmoid nodules and infiltration was 91.1% and 88.9%. Conclusions Both techniques showed satisfactory results. TVS appears a powerful, simple, feasible, cost effective tool for preoperative staging of DIE. CE-MR-C is an “X Ray free” technique, which could be reserved for cases with deep infiltrating rectosigmoid lesions, for the prediction of stenosis and involvement of the upper part of colon and small intestine.

Reprod Sci.2012 Apr 23. [Epub ahead of print]

Stress Exacerbates Endometriosis Manifestations and Inflammatory Parameters in an Animal Model.

Cuevas M, Flores I, Thompson KJ, Ramos-Ortolaza DL, Torres-Reveron A, Appleyard CB.

Abstract

Women with endometriosis have significant emotional distress; however, the contribution of stress to the pathophysiology of this disease is unclear. We used a rat model of endometriosis to examine the effects of stress on the development of this condition and its influence on inflammatory parameters. Female Sprague-Dawley rats were subjected to swim stress for 10 consecutive days prior to the surgical induction of endometriosis by suturing uterine horn implants next to the intestinal mesentery (endo-stress). Sham-stress animals had sutures only, and an endo-no stress group was not subjected to the stress protocol. At the time of sacrifice on day 60, endometriotic vesicles were measured and colons assessed for macroscopic and microscopic damage. Colonic tissue and peritoneal fluid were collected for inflammatory cell analysis. Endometriosis, regardless of stress, produced a decrease in central corticotropin-releasing factor immunoreactivity, specifically in the CA3 subregion of the hippocampus. Prior exposure to stress increased both the number and severity of vesicles found in animals with endometriosis. Stress also increased colonic inflammation, motility, myeloperoxidase levels, and numbers of mast cells. In summary, prior stress may contribute to the development and severity of endometriosis in this animal model through mechanisms involving cell recruitment (eg, mast cells), release of inflammatory mediators, and deregulation of hypothalamic-pituitary axis responses in the hippocampus.

Fertil Steril.2012 Apr 21. [Epub ahead of print]

Activated glucocorticoid and eicosanoid pathways in endometriosis.

Monsivais D, Bray JD, Su E, Pavone ME, Dyson MT, Navarro A, Kakinuma T, Bulun SE.

Source

Division of Reproductive Biology Research, Northwestern University, Chicago, Illinois.

Abstract

OBJECTIVE:

To define altered gene expression networks in endometriosis.

DESIGN:

Experiments using endometriotic tissues and primary cells.

SETTING:

Division of Reproductive Biology Research, Northwestern University.

PATIENT(S):

Premenopausal women.

INTERVENTION(S):

Matched samples of eutopic endometrium and ovarian endometriosis (n = 8 patients) were analyzed by microarray and verified in a separate set of tissues (n = 6 patients). Experiments to define signaling pathways were performed in primary endometriotic stromal cells (n = 12 patients).

MAIN OUTCOMES MEASURE(S):

Using a genome-wide in vivo approach, we identified 1,366 differentially expressed genes and a new gene network favoring increased glucocorticoid levels and action in endometriosis.

RESULT(S):

Transcript and protein levels of 11β-hydroxysteroid dehydrogenase (HSD11B1), which produces cortisol, the biologically active glucocorticoid, were strikingly higher, whereas messenger RNA (mRNA) levels of the cortisol-degrading HSD11B2 enzyme were significantly lower in endometriotic tissue. Glucocorticoid receptor mRNA and protein levels were significantly higher in endometriosis. The inflammatory cytokine tumor necrosis factor robustly induced mRNA and protein levels of HSD11B1 and glucocorticoid receptor but suppressed HSD11B2 mRNA in primary endometriotic stromal cells, suggesting that tumor necrosis factor stimulates cortisol production and action. We also uncovered a subset of genes critical for prostaglandin synthesis and degradation, which favor high eicosanoid levels and activity in endometriosis.

CONCLUSION(S):

The proinflammatory milieu of the endometriotic lesion stimulates cortisol synthesis and action in endometriotic lesions.

Gynecol Oncol.2012 Apr 21. [Epub ahead of print]

Clear cell carcinoma of the ovary: A review of the literature.

Del Carmen MG, Birrer M, Schorge JO.

Source

Division of Gynecologic Oncology, Vincent Obstetrics and Gynecology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Abstract

OBJECTIVE:

Different histologic types of epithelial ovarian cancer may represent different diseases with unique clinical and molecular characteristics. Clear cell carcinoma (CCC) of the ovary has been reported as having a worse prognosis than high grade serous epithelial ovarian cancer (EOC). This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with ovarian CCC.

METHODS:

MEDLINE was searched for all research articles published in English between January 01, 1977 and January 30, 2012 which reported on patients diagnosed with ovarian CCC. Given the rarity of this tumor, studies were not limited by design or number of reported patients.

RESULTS:

Ovarian CCC tumors represent 5-25% of ovarian cancers. Its histologic diagnosis can be challenging, resulting often times in misclassification of these tumors. Ovarian CCC tends to present at earlier stages and has been associated with endometriosis, ARID1A and PIK3CA mutations. When compared to stage-matched controls, patients with early-stage ovarian CCCs may have a better prognosis than patients with high-grade serous tumors. For those with advanced stage disease, high-grade serous histology confers a better prognosis than ovarian CCC. Patients with Stage IC-IV have a relatively poor prognosis and efforts should center in discovery of more effective treatment strategies

CONCLUSIONS:

Ovarian CCC is a biologically distinct entity, different from high-grade serous EOC. Future studies should explore the role of targeted therapies in the management of ovarian CCC.

Reprod Biol Endocrinol.2012 Apr 20;10(1):30. [Epub ahead of print]

Expression of the G protein-coupled estrogen receptor (GPER) in endometriosis: a tissue microarray study.

Samartzis N, Samartzis EP, Noske A, Fedier A, Dedes KJ, Caduff R, Fink D, Imesch P.

Abstract

ABSTRACT:

BACKGROUND:

The G protein-coupled estrogen receptor (GPER) is thought to be involved in non-genomic estrogen responses as well as processes such as cell proliferation and migration. In this study, we analyzed GPER expression patterns from endometriosis samples and normal endometrial tissue samples and compared these expression profiles to those of the classical sex hormone receptors.

METHODS:

A tissue microarray, which included 74 samples from different types of endometriosis (27 ovarian, 19 peritoneal and 28 deep-infiltrating) and 30 samples from normal endometrial tissue, was used to compare the expression levels of the GPER, estrogen receptor (ER)-alpha, ER-beta and progesterone receptor (PR). The immunoreactive score (IRS) was calculated separately for epithelium and stroma as the product of the staining intensity and the percentage of positive cells. The expression levels of the hormonal receptors were dichotomized into low (IRS < 6) and high (IRS > =6) expression groups.

RESULTS:

The mean epithelial IRS (+/standard deviation, range) of cytoplasmic GPER expression was 1.2 (+/1.7, 0-4) in normal endometrium and 5.1 (+/3.5, 0-12) in endometriosis (p < 0.001), of nuclear GPER 6.4 (+/2.6, 0-12) and 6.8 (+/2.9, 2-12; p = 0.71), of ER-alpha 10.6 (+/2.4, 3-12) and 9.8 (+/3.0, 2-12; p = 0.26), of ER-beta 2.4 (+/2.2; 0-8) and 5.6 (+/2.6; 0-10; p < 0.001), and of PR 11.5 (+/1.7; 3-12) and 8.1 (+/4.5; 0-12; p < 0.001), respectively. The mean stromal IRS of nuclear GPER expression was 7.7 (+/3.0; 2-12) in endometrium and 10.8 (+/1.7; 6-12) in endometriosis (p < 0.001), of ER-alpha 8.7 (+/3.1; 2-12) and 10.6 (+/2.4; 2-12; p = 0.001), of ER-beta 1.8 (+/2.0; 0-8) and 5.4 (+/2.5; 0-10; p < 0.001), and of PR 11.7 (+/0.9; 8-12) and 10.9 (+/2.0; 3-12; p = 0.044), respectively. Cytoplasmic GPER expression was not detectable in the stroma of endometrium and endometriosis. The observed frequency of high epithelial cytoplasmic GPER expression levels was 50% (n = 30/60) in the endometriosis and none (0/30) in the normal endometrium samples (p < 0.001). High epithelial cytoplasmic GPER expression levels were more frequent in endometriomas (14/20, 70%; p = 0.01), as compared to peritoneal (9/18, 50%) or deep-infiltrating endometriotic lesions (7/22, 31.8%). The frequency of high stromal nuclear GPER expression levels was 100% (n = 74/74) in endometriosis and 76.7% (n = 23/30) in normal endometrium (p < 0.001). The frequency of high epithelial nuclear GPER expression levels did not differ between endometriosis and normal endometrium.

CONCLUSIONS:

The present data indicate a unique GPER expression pattern in endometriosis, especially in endometriomas as compared to the normal endometrium. The overexpression of GPER in endometriotic lesions suggests a potential role for GPER in the hormonal regulation of endometriosis, which should be taken into consideration for future hormonal treatment strategies.

BMC Womens Health.2012 Apr 19;12(1):9. [Epub ahead of print]

Treatment of endometriosis in different ethnic populations: a meta-analysis of two clinical trials.

Gerlinger C, Faustmann T, Hassal JJ, Seitz C.

Abstract

ABSTRACT: Approaches to the treatment of endometriosis vary worldwide, but studies comparing endometriosis medications in different ethnic groups are rare. A systematic literature search identified two studies directly comparing dienogest (DNG) versus gonadotropin-releasing hormone (GnRH) analogues in European and Japanese populations. Meta-analysis of visual analogue scale scores revealed no heterogeneity in response between the trials, indicating equivalent efficacy of DNG and GnRH analogues for endometriosis-related pain across populations. DNG was significantly superior to GnRH analogues for bone mineral density change in both trials, but significant heterogeneity between the studies may indicate ethnic differences in physiology.

Gynecol Obstet Fertil.2012 Apr 19. [Epub ahead of print]

General practitioners and the challenge of endometriosis screening and care: Results of a survey.

[Article in French]

Quibel A, Puscasiu L, Marpeau L, Roman H.

Source

1, rue Roger-Gobbe, 76230 Bois Guillaume, France.

Abstract

OBJECTIVE:

To evaluate the knowledge of general practitioners concerning the endometriosis diagnostic and care.

POPULATION AND METHODS:

Survey enrolling 100 general practitioners of the 76th Seine Maritime French department (region of Upper Normandy) who usually perform gynaecological follow up, asked to answer an irreversible 36 item step-by-step questionnaire.

RESULTS:

Among them, 44% perform more than one gynaecological consultation each week. They were 63% to feel ill at ease in the diagnosis and follow up of women presenting with endometriosis. One half of physicians could not cite three main symptoms of the disease out of dysmenorrhea, dyspareunia, chronic pelvic pain and infertility. Only 38% of general practitioners perform a clinical gynaecological examination when they suspect the endometriosis, and 28% of them recommended MRI to confirm the diagnosis. They are 24% to refer the patient without delay, but only 52% to the universitary hospital, which is the tertiary regional referral center, while 68% of them refer to a fellow practicing in a private facility. They were 64% to believe that therapeutic amenorrhea is on the bottom of the medical therapy. General practitioners were more likely to accurately answer the questionnaire when they attended gynaecological advanced courses during previous 5 years and when they followed up more than three patients previously managed for endometriosis.

DISCUSSION AND CONCLUSION:

General practitioners’ knowledge about endometriosis is limited, with possible direct consequences on the delay of the diagnosis. The attendance of gynaecological advanced courses and the exchange of information between gynaecologic surgeons and general practitioners who follow up the patients appear to be two-way to improve the accuracy of the answers to the questionnaire.

J Comp Pathol.2012 Apr 18. [Epub ahead of print]

Spontaneous Endometriosis in a Mandrill (Mandrillus sphinx).

Nakamura S, Ochiai K, Ochi A, Ito M, Kamiya T, Yamamoto H.

Source

Laboratory of Comparative Pathology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.

Abstract

A 25-year-old female mandrill (Mandrillus sphinx) died after exhibiting weakness and recumbency with serosanguineous ascites. Gross findings included haemoperitoneum and multifocal to diffuse serosal thickening with petechiae and ecchymoses throughout the peritoneum. The uterus was covered entirely with large blood clots and was adherent to the ovaries and pelvic wall. Microscopical and immunohistochemical examination revealed extra- and intra-uterine growth of ectopic endometrial tissue with marked fibrosis. The ectopic endometrial tissues predominantly consisted of stromal cells expressing CD10 and progesterone receptor and variably-sized glands lined by the epithelium with occasional slight expression of oestrogen receptor α. A diagnosis of endometriosis was made. This is the first report of naturally occurring endometriosis in a mandrill.

Am J Reprod Immunol.2012 Apr 17. doi: 10.1111/j.1600-0897.2012.01136.x. [Epub ahead of print]

The Association Between Endometriosis and Polymorphisms in the Interleukin-1 Family Genes in Korean Women.

Chun S, Kim H, Ku SY, Suh CS, Kim SH, Kim JG.

Source

Department of Obstetrics and Gynecology, College of Medicine, Inje University, Haeundae Paik Hospital, Busan, Korea.

Abstract

PROBLEM:

To investigate the association between polymorphisms of the interleukin-1 (IL-1) family genes and endometriosis in Korean women.

METHOD OF STUDY:

In this case-control study, the IL-1α -889C>T, IL-1 receptor antagonist (IL-1RA) 86-bp microsatellite, IL-1 receptor 1 (IL-1R1) 52C>A, 294C>T, 1498T>C, 1632A>G, IL-1R2 rs2072472 C>T and rs7561460 C>T polymorphisms were analyzed in women with (n = 138) and without (n = 214) endometriosis using restriction fragment length polymorphism (RFLP) analysis, TaqMan assay, or DNA sequencing. Serum IL-1α, soluble IL-1RA (sIL-1RA), and sIL-1R2 levels were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS:

Among the polymorphisms measured, the 1498T>C polymorphisms in the IL-1R1 gene were found to be related with early-stage endometriosis but not with advanced-stage endometriosis. The genotypes with at least one T allele (CT + TT) were less frequently observed in early-stage endometriosis compared with normal controls (OR = 0.44, 95% CI = 0.22-0.87, P = 0.02). Serum sIL-1R2 levels were significantly lower (P < 0.01) in women with endometriosis than in normal controls, whereas no difference in serum sIL-1RA levels between these two groups was noted. The single and haplotype genotypes of the IL-1R2 and IL-1RA microsatellite polymorphisms were not related with these serum levels.

CONCLUSION:

The IL-1R1 1498T>C polymorphism is associated with early-stage endometriosis in Korean women.

Environ Sci Technol.2012 Apr 17;46(8):4624-32. Epub 2012 Mar 29.

Urinary concentrations of benzophenone-type UV filters in U.S. women and their association with endometriosis.

Kunisue T, Chen Z, Buck Louis GM, Sundaram R, Hediger ML, Sun L, Kannan K.

Source

Wadsworth Center, New York State Department of Health, School of Public Health, State University of New York at Albany, Empire State Plaza, P.O. Box 509, Albany, New York 12201-0509, United States.

Abstract

Benzophenone (BP)-type UV filters are widely used in a variety of personal care products for the protection of skin and hair from UV irradiation. Despite the estrogenic potencies of BP derivatives, few studies have examined the occurrence of these compounds in human matrices. Furthermore, associations among exposure to these compounds and estrogen-dependent diseases (such as endometriosis) have not been examined previously. In this study, we determined the concentrations of five BP derivatives, 2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4OH-BP), 2,2′-dihydroxy-4-methoxybenzophenone (2,2’OH-4MeO-BP), 2,2′,4,4′-tetrahydroxybenzophenone (2,2′,4,4’OH-BP), and 4-hydroxybenzophenone (4OH-BP), in urine collected from 625 women in Utah and California, using liquid chromatography (LC)-tandem mass spectrometry (MS/MS). The association of urinary concentrations of BP derivatives with an increase in the odds of a diagnosis of endometriosis was examined in 600 women who underwent laparoscopy/laparotomy (n = 473: operative cohort) or pelvic magnetic resonance imaging (n = 127: population cohort), during 2007-2009. 2OH-4MeO-BP, 2,4OH-BP, and 4OH-BP respectively were detected in 99.0%, 93.3%, and 83.8% of the urine samples analyzed, whereas the detection rates for 2,2′,4,4’OH-BP and 2,2’OH-4MeO-BP were below 6.0%. Significant regional differences (higher concentrations in California) and monthly variations (higher concentrations in July and August) were found for urinary concentrations of 2OH-4MeO-BP and 2,4OH-BP. In addition, urinary concentrations of 2OH-4MeO-BP and 2,4OH-BP tended to be higher in more affluent, older, and leaner women. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for the urinary concentrations of BP derivatives and the odds of an endometriosis diagnosis; ORs increased across quartiles of 2OH-4MeO-BP and 2,4OH-BP concentrations, but a significant trend was observed only between 2,4OH-BP and the odds of an endometriosis diagnosis in the operative cohort (OR = 1.19; 95% CI = 1.01, 1.41). When women in the highest quartile of 2,4OH-BP concentrations were compared with women in the first three quartiles, the OR increased considerably (OR = 1.65; 95% CI = 1.07, 2.53). Given that 2,4OH-BP possesses an estrogenic activity higher than that of 2OH-4MeO-BP, our results invite the speculation that exposure to elevated 2,4OH-BP levels may be associated with endometriosis.

J Med Chem.2012 Apr 12;55(7):3307-18. Epub 2012 Mar 16.

Lead optimization of 17β-HSD1 inhibitors of the (hydroxyphenyl)naphthol sulfonamide type for the treatment of endometriosis.

Henn C, Einspanier A, Marchais-Oberwinkler S, Frotscher M, Hartmann RW.

Source

Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C2 3, D-66041 Saarbrücken, Germany.

Abstract

The reduction of estrone to estradiol, the most potent estrogen in human, is catalyzed by 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1). A promising approach for the treatment of estrogen-dependent diseases is the reduction of intracellular estradiol formation by inhibition of 17β-HSD1. For the species-specific optimization of the (hydroxyphenyl)naphthols, a combinatorial approach was applied and enhanced by a focused synthesis that resulted in the aromatic-substituted (hydroxyphenyl)naphthol sulfonamides. Rigidification of 12 led to the 4-indolylsulfonamide 30, which is a highly active and selective human 17β-HSD1 inhibitor, as well as a highly potent and selective inhibitor of 17β-HSD1 from Callithrix jacchus. It shows no affinity to the estrogen receptors α and β and good intracellular activity (T47D). Thus, compound 30 shows good properties for further ADMET studies and might be a candidate for the in vivo proof of concept in C. jacchus.

Arch Gynecol Obstet.2012 Apr 6. [Epub ahead of print]

Massive hemothorax due to diaphragmatic endometriosis after a laparoscopic cystectomy of an ovarian endometrioma in a patient without a history of thoracic endometriosis.

Kyo S, Takakura M, Nishida S, Ozaki S, Oda M, Inoue M.

Source

Department of Obstetrics and Gynecology, Kanazawa University School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan, satoruky@med.kanazawa-u.ac.jp.

Abstract

BACKGROUND:

Severe hemothorax is a rare complication after laparoscopic surgery for endometriosis, and the causes and proper management are not well understood.

CASE:

We report here the extremely rare case with massive hemothorax after laparoscopic surgery for ovarian endometrioma. A 40-year-old woman, gravida 1, para 1, underwent laparoscopic cystectomy of ovarian endometrioma. On postoperative day 2, she had progressive anemia (Hb 5.3) as well as dyspnea. A chest X-ray and computed tomography showed massive fluid collection in the right thoracic cavity, suggestive of intrapleural bleeding.

TREATMENT:

Thoracoscopic operation was performed and a total of 930 ml of blood retention in the right thoracic cavity was found. Scattered small endometriotic lesions were present on the pleural surface of the right diaphragm; pulsatile active bleeding was confirmed from one of these. Furthermore, two endometriotic lesions had perforated into the intraperitoneal cavity. The diaphragm containing bleeding spots was thoracoscopically resected and sutured. After thoracoscopic surgery, the dyspnea and anemia resolved. On postoperative day 5, the patient left the hospital.

CONCLUSION:

The present report reminds us of the importance of paying special attention to postoperative-thoracic complications caused by diaphragmatic endometriosis if the patient shows respiratory symptoms.

Abdom Imaging.2012 Apr 4. [Epub ahead of print]

Anatomical localization of deep infiltrating endometriosis: 3D MRI reconstructions.

Giusti S, Forasassi F, Bastiani L, Cela V, Pluchino N, Ferrari V, Fruzzetti E, Caramella D, Bartolozzi C.

Source

Department of Radiology, University of Pisa, Pisa, Italy, s.giusti@med.unipi.it.

Abstract

PURPOSE:

The goal of this study was to determine the accuracy of three-dimensional (3D) MRI reconstructions obtained with segmentation technique in the preoperative assessment of deep infiltrating endometriosis (DIE) and in particular to evaluate rectosigmoid and bladder wall involvement.

MATERIALS AND METHODS:

Institutional review board approval for this study was obtained, and each patient gave written informed consent. Fifty-seven consecutive patients with diagnosis of DIE who had undergone pelvic MRI at 1.5 T before surgery between 2007 and 2011, were retrospectively evaluated and 3D post-processed in order to obtain a detailed mapping of DIE. A blinded reader interpreted images. MRI results were compared with surgical findings and were scored by using a four-point scale (0_3 score).

RESULTS:

36/57 patients with symptomatic DIE underwent surgery: 18/36 had endometriotic nodules infiltrating the rectouterine pouch, 12/36 the vesicouterine pouch, and 6/36 the rectovaginal pouch. The sensitivity of MRI and 3D MRI vs. surgery was, respectively, 64% vs. 83%; diagnostic accuracy of 3D MRI respect to MRI alone was 86% vs. 67% for localization; 86% vs. 67% for dimension; 79% vs. 58% for rectosigmoid infiltration; 92% vs. 75% for bladder infiltration.

CONCLUSIONS:

In this preliminary study, 3D MRI reconstructions obtained with semi-automatic method of segmentation provided encouraging results for staging DIE preoperatively. In fact, the addition of 3D MRI reconstructions improved diagnostic accuracy and staging of DIE providing the exact volume of the lesions and enabling a precise mapping of these before surgery.

Biol Reprod.2012 Apr 4. [Epub ahead of print]

Simvastatin Decreases Invasiveness of Human Endometrial Stromal Cells.

Sokalska A, Cress A, Bruner-Tran KL, Osteen KG, Taylor HS, Ortega I, Duleba AJ.

Abstract

Recently we have reported that statins, the competitive inhibitors of the key enzyme regulating the mevalonate pathway, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), decrease proliferation of human endometrial stromal (HES) cells. Furthermore, we found that simvastatin treatment reduces the number and the size of endometrial implants in a nude mouse model of endometriosis. The present study was undertaken to investigate the effect of simvastatin on HES cell invasiveness and on expression of selected genes relevant to invasiveness: matrix metalloproteinases (MMPs) -2 and -3, tissue inhibitor of matrix metalloproteinases-2 (TIMP-2) and CD44. Since statin-induced inhibition of HMGCR reduces the production of substrates for isoprenylation (geranylgeranyl pyrophosphate, GGPP and farnesyl pyrophosphate, FPP), effects of GGPP and FPP were also evaluated. Simvastatin induced a concentration-dependent reduction of invasiveness of HES cells. This effect of simvastatin was abrogated by geranylgeranyl pyrophosphate (GGPP) but not by farnesyl pyrophosphate. Simvastatin also reduced mRNA levels of MMP-2, MMP-3 and CD44 but increased TIMP-2 mRNA; all these effects of simvastatin were partly or entirely reversed in the presence of GGPP. The present findings provide a novel mechanism of action of simvastatin on endometrial stroma that may explain reduction of endometriosis in animal models of this disease. Furthermore, the presently described effects of simvastatin are likely mediated, at least in part by, inhibition of geranylgeranylation.

J Atheroscler Thromb.2012 Apr 4. [Epub ahead of print]

Hydrogen Peroxide-Inducible Clone 5 (Hic-5) as a Potential Therapeutic Target for Vascular and Other Disorders.

Kim-Kaneyama JR, Lei XF, Arita S, Miyauchi A, Miyazaki T, Miyazaki A.

Source

Department of Biochemistry, Showa University School of Medicine.

Abstract

Hydrogen peroxide-inducible clone-5 (Hic-5) is a focal adhesion scaffold protein primarily expressed in vascular and visceral smooth muscle cells. We recently generated mice lacking Hic-5, which grew with no apparent abnormality (Kim-Kaneyama J, et al. J Mol Cell Cardiol. 2011;50(1):77-86). However, we discovered that recovery of arterial media following vascular injury is delayed significantly in Hic-5 knockout mice consequent to enhanced apoptosis of cultured vascular smooth muscle cells after mechanical stress; thus, Hic-5 is regarded as a novel factor in vascular remodeling. The Hic-5 gene is also induced by transforming growth factor-β, a well-known accelerator in fibrosis. Hic-5 involvement in various fibrotic disorders, e.g., scar formation, keloid formation and glomerulosclerosis, has been proposed. siRNA silencing of Hic-5 in a breast cancer cell line reduces its invasiveness; moreover, Hic-5 serves as a steroid hormone co-activator and likely participates in endometriosis and prostate cancer. Thus, functional characterization of Hic-5 in various pathophysiological conditions may afford novel mechanistic insights into a wide variety of diseases.

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