Minerva Med. 2012 Feb;103(1):63-72.

Urological morbidity of colorectal resection for endometriosis.

Daraï E, Zilberman S, Touboul C, Chereau E, Rouzier R, Ballester M.

Source

Service de Gynécologie-Obstétrique, Hôpital Tenon, AP-HP, Université Pierre et Marie Curie, Paris 6, France – emile.darai@tnn.aphp.fr.

Abstract

Colorectal resection for endometriosis is a major operation exposing patients to the risk of severe digestive and urological complications. The objective of this review is to evaluate surgery-related urological morbidity of which little is known to date. We searched MEDLINE for articles published on colorectal resection for endometriosis between 1998 and March 2011 using the following terms: “bowel”, “rectal”, “colorectal”, “rectovaginal”, “rectosigmoid”, “resection” and “endometriosis”. We were not able to perform a meta- analysis due to a lack of complete data on urological complications so have focused this review on voiding dysfunction and ureteral injury. Thirty-two articles reporting on 3047 colorectal resections for endometriosis including 1930 segmental resections, 271 discoid resections and 846 rectal shavings were analysed. For voiding dysfunction, 28 series including 2563 colorectal resections were available. Postoperative voiding dysfunction varied from 0% to 30.4% with a mean value of 3.4% (73/2118). Fourteen series reported an incidence of ureterolysis comprising between 8.5% and 100% with a mean value of 46% (815/1772 patients). The risk of urinary fistulae evaluated in 26 series was estimated at 0.9% (24/2581 patients). Only one case of hydronephrosis was reported in 9 series including 1256 patients (0.07%). The incidence of urological morbidity associated with colorectal endometriosis is poorly documented and probably underestimated due to the short follow-up reported in the series. Moreover, as complication rates varied widely according to the type of surgery and the experience of the teams, further studies are required to identify risk factors of urological morbidity so as to adequately inform patients.

Fertil Steril. 2012 Jan 24. [Epub ahead of print]

Sphingosine pathway deregulation in endometriotic tissues.

Santulli P, Marcellin L, Noël JC, Borghese B, Fayt I, Vaiman D, Chapron C, Méhats C.

Source

Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, AP- HP, Groupe Hospitalier Universitaire Ouest, Centre Hospitalier Universitaire Cochin Saint Vincent de Paul, Department of Gynecology Obstetrics II and Reproductive Medicine, France; Inserm, Unité de recherche U1016, Institut Cochin, Université Paris Descartes, Sorbonne Paris Cité, CNRS (UMR 8104), France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, Laboratoire d’immunologie, EA 1833 AP-HP Hôpital Cochin, Paris Cedex 14, France.

Abstract

OBJECTIVE:

To investigate key genes expression of the sphingosine-1-phosphate pathway in endometriotic tissues.

DESIGN:

A case-control laboratory study.

SETTING:

Tertiary care university hospital.

PATIENT(S):

A total of 31 women, with (n = 16) and without (n = 15) endometriosis took part in the study.

INTERVENTION(S):

After surgical excision with pathological analysis, endometrial specimens were obtained from women affected or not by endometriosis.

MAIN OUTCOME MEASURE(S):

SPHK1-2, SGPP1-2, SGPL1, SPHKAP, and S1PR1-5 messenger RNA expression by quantitative real-time polymerase chain reaction (PCR) in the endometrium of 15 disease-free women, 16 eutopic and 16 ectopic endometrium of endometriosis-affected women. The S1PR1 and S1PR2 expression were further investigated by immunohistochemistry.

RESULT(S):

The SGPP2 expression was decreased in eutopic and ectopic endometrium of endometriosis-affected women (1.7- and 16.7-fold, respectively). The SGPP1, weakly expressed in healthy endometrium, is up-regulated in endometriosis-affected women (11.9- and 64.7-fold, respectively), but its expression remains low. The SGPL1 expression was decreased in ectopic endometrium (3.3-fold) and SPHKAP expression was increased in ectopic endometrium (112.6-fold) compared with endometrium of disease-free women. In endometriosis-affected women, S1PR3 expression was decreased in eutopic and ectopic endometrium (2.1- and 6.3-fold, respectively); S1PR2 and S1PR1 expression was increased in eutopic (2.5-fold) and ectopic endometrium (2.6-fold). These increases were confirmed at the protein levels by immunohistochemistry.

CONCLUSION(S):

Expression of the enzymes implicated in the regulation of the sphingosine-1-phosphate level balance and of its receptors is overall heavily deregulated in endometriotic lesions in favor of a decreased sphingosine-1-phosphate catabolism. Our results plead for a role of the sphingosine pathway in establishing and survival of endometriotic lesions.

Aust N Z J Obstet Gynaecol. 2012 Jan 25. doi: 10.1111/j.1479-828X.2011.01405.x. [Epub ahead of print]

Identification of endometriosis-related genes by representational difference analysis of cDNA.

Chen Q, Zhang C, Chen Y, Lou J, Wang D.

Source

Department of Obstetrics & Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, China.

Abstract

BACKGROUND:

Accumulated evidence reveals that abnormally expressed genes in eutopic endometrium of endometriosis play a critical role in the pathogenesis of endometriosis.

AIMS:

Identification of endometriosis-related genes for further revealing the pathogenesis of endometriosis and offering the basis for developing the molecular-targeted diagnosis and therapy of endometriosis.

METHODS:

Forty women with endometriosis and forty control women without endometriosis during their secretory phase were selected for this study. cDNA representational difference analysis (cDNA-RDA) was performed to screen the up-regulated genes in eutopic endometrium samples of endometriosis (n = 10) compared with the controls (n = 10). To validate the results, MAT2A, the most abundantly expressed gene, was selected to detect mRNA and protein levels between eutopic endometrium of endometriosis (n = 40) and controls (n = 40) using immunohistochemistry, real-time fluorescent quantitative PCR and Western blotting.

RESULTS:

Ten up-regulated genes were identified in eutopic endometria of endometriosis compared with controls. Among these genes, COX-2, BRAF, NRAS and CFL1 have already been reported to be associated with the endometriosis in previous studies. MAT2A, SEPT9, ATAD3A and CADM2 have been reported to be involved in other diseases but not in endometriosis. NAA15 and CCDC21 have not reported in any diseases. Further study showed that MAT2A protein was localised in both endometrial glandular and stromal cells. Compared with controls, the mRNA and protein levels of MAT2A were significantly higher in eutopic endometrium of endometriosis (P < 0.05).

CONCLUSIONS:

cDNA-RDA can be used to effectively identify the endometriosis-related genes, which can provide novel experimental data and further understand the pathogenesis of endometriosis.

Eur J Endocrinol. 2012 Jan 24. [Epub ahead of print]

Vitamin D and fertility-a systematic review.

Lerchbaum E, Obermayer-Pietsch BR.

Source

E Lerchbaum, Department of Internal Medicine, Divison of Endocrinology and Nuclear Medicine, Medical University Graz, Graz, 8036, Austria.

Abstract

Background: Vitamin D has been well-known for its function in maintaining calcium and phosphorus homeostasis and promoting bone mineralization. There is some evidence, that in addition to sex steroid hormones, the classic regulators of human reproduction, vitamin D also modulates reproductive processes in women and men.Aim: The aim of this review was to assess studies that evaluated the relationship between vitamin D and fertility in women and men as well as in animals.Methods: We performed a systematic literature search in Pubmed for relevant English language publications published until October 2011.Results and Discussion: The vitamin D receptor (VDR) and vitamin D metabolizing enzymes are found in reproductive tissues of women and men. VDR knockout mice have significant gonadal insufficiency, decreased sperm count and motility, and histological abnormalities of testis, ovary and uterus. Moreover, we present evidence that vitamin D is involved in female reproduction including in-vitro fertilization (IVF) outcome (clinical pregnancy rates) and polycystic ovary syndrome (PCOS). In PCOS women, low 25-hydroxyvitamin D (25(OH)D) levels are associated with obesity, metabolic and endocrine disturbances and vitamin D supplementation might improve menstrual frequency and metabolic disturbances in those women. Moreover, vitamin D might influence steroidogenesis of sex hormones (estradiol and progesterone) in healthy women and high 25(OH)D levels might be associated with endometriosis. In men, vitamin D is positively associated with semen quality and androgen status. Moreover, vitamin D treatment might increase testosterone levels. Testiculopathic men show low CYP21R expression, 25(OH)D levels and osteoporosis despite normal testosterone levels.

Respir Care. 2012 Jan 23. [Epub ahead of print]

Catamenial Pneumothorax Due to Bilateral Pulmonary Endometriosis.

Fang HY, Jan CI, Chen CK, Chen WT.

Abstract

Coexistance of catamenial pneumothorax and hemoptysis is rare. We present a case of catamenial pneumothorax due to bilateral pulmonary endometriosis in a 45 year-old woman. The patient presented with a 3-year history of intermittent productive cough with blood-tinged sputum, chronic anemia, loss of appetite and general weakness associated with menstruation. Three years prior to this presentation the patient had undergone a sigmoidectomy as treatment for endometriosis of the sigmoid colon with bleeding. Chest radiographs and computer tomography (CT) scan revealed multiple nodules in both lung parenchyma and recurrent pneumothorax. CT-guided biopsy revealed chronic inflammation of those pulmonary nodules and laboratory studies disclosed elevated serum levels of CA19-9 and CA-125. Thoracoscopic wedge resection of the pulmonary nodules was performed and histopathological examination of the resected nodules revealed endometriosis. At one-year follow-up, there was no evidence of recurrence of gastrointestinal bleeding or pneumothorax.

Semin Reprod Med. 2012 Jan;30(1):39-45. Epub 2012 Jan 23.

Role of Estrogen Receptor-β in Endometriosis.

Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, Tokunaga H, Su EJ.

Source

Division of Reproductive Biology Research, Department Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

Abstract

Endometriosis is an estrogen-dependent disease. The biologically active estrogen, estradiol, aggravates the pathological processes (e.g., inflammation and growth) and the symptoms (e.g., pain) associated with endometriosis. Abundant quantities of estradiol are available for endometriotic tissue via several mechanisms including local aromatase expression. The question remains, then, what mediates estradiol action. Because estrogen receptor (ER)β levels in endometriosis are >100 times higher than those in endometrial tissue, this review focuses on this nuclear receptor. Deficient methylation of the ERβ promoter results in pathological overexpression of ERβ in endometriotic stromal cells. High levels of ERβ suppress ERα expression. A severely high ERβ-to-ERα ratio in endometriotic stromal cells is associated with suppressed progesterone receptor and increased cyclo-oxygenase-2 levels contributing to progesterone resistance and inflammation. ERβ-selective estradiol antagonists may serve as novel therapeutics of endometriosis in the future.

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Arch Gynecol Obstet. 2012 Jan 24. [Epub ahead of print]

c-kit/CD 117 positive cells in the myometrium of pregnant women and those with uterine endometriosis.

Horn LC, Meinel A, Hentschel B.

Source

Division of Breast, Gynecologic & Perinatal Pathology, Institute of Pathology, University of Leipzig, Liebigstrasse 26, Leipzig, 04103, Germany, hornl@medizin.uni-leipzig.de.

Abstract

PURPOSE:

Abnormal myometrial motility may play a role in the pathogenesis of endometriosis. Uterine contractility is a major contribution to labour. Myometrial motility might be controlled by CD 117-positive uterine smooth muscle cells.

METHODS:

Myometrial tissues from 8 cases with uterine endometriosis, 9 pregnant uteri (31.1 ± 8.7 weeks of gestation), 10 cases from non-pregnant pre-menopausal and 9 cases from post-menopausal women were immunohistochemically evaluated using a polyclonal antibody against c-kit/CD 117. The number of CD 117 positive cells was counted within 10 microscopic high power fields (×400) and compared with the clinical diagnoses.

RESULTS:

Overall, a mean number of 15.7 (range 0-43) CD 117-positive cells within the myometrium was seen. Significant highest count occurred in the myometrium of non-pregnant pre-menopausal women without uterine endometriosis (30.78 ± 9.52), followed by post-menopausal women (15.5 ± 8.37) and those with uterine endometriosis (9.98 ± 4.9; p ≤ 0.01). The lowest count of CD 117-positive cells was seen in pregnant uteri (4.09 ± 2.33; p < 0.001).

CONCLUSIONS:

The lowest count of CD 117-positive cells was seen in the myometrium of pregnant women suggesting a role of preventing premature uterine contractility. There is no increase of CD 117-positive cells in the myometrium of women affected by uterine endometriosis.

Obstet Gynecol. 2012 Feb;119(2, Part 1):276-285.

Proteomics Analysis of Plasma for Early Diagnosis of Endometriosis.

Fassbender A, Waelkens E, Verbeeck N, Kyama CM, Bokor A, Vodolazkaia A, Van de Plas R, Meuleman C, Peeraer K, Tomassetti C, Gevaert O, Ojeda F, De Moor B, Dʼhooghe T.

Source

From the Department of Obstetrics and Gynaecology, Leuven University Fertility Centre, University Hospital Gasthuisberg, the Department of Molecular Cell Biology, Campus Gasthuisberg, ProMeta, Interfaculty Centre for Proteomics and Metabolomics, O&N2, and the IBBT-KU Leuven Future Health Department, Leuven, Belgium; the Division of Reproductive Biology, Institute of Primate Research, Karen, Nairobi, Kenya; the Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary; and the Department of Electrical Engineering, ESAT-SCD, Katholieke Universiteit Leuven, Leuven, Belgium.

Abstract

OBJECTIVE:

To test the hypothesis that differential surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein or peptide expression in plasma can be used in infertile women with or without pelvic pain to predict the presence of laparoscopically and histologically confirmed endometriosis, especially in the subpopulation with a normal preoperative gynecologic ultrasound examination.

METHODS:

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry analysis was performed on 254 plasma samples obtained from 89 women without endometriosis and 165 women with endometriosis (histologically confirmed) undergoing laparoscopies for infertility with or without pelvic pain. Data were analyzed using least squares support vector machines and were divided randomly (100 times) into a training data set (70%) and a test data set (30%).

RESULTS:

Minimal-to-mild endometriosis was best predicted (sensitivity 75%, 95% confidence interval [CI] 63-89; specificity 86%, 95% CI 71-94; positive predictive value 83.6%, negative predictive value 78.3%) using a model based on five peptide and protein peaks (range 4.898-14.698 m/z) in menstrual phase samples. Moderate-to-severe endometriosis was best predicted (sensitivity 98%, 95% CI 84-100; specificity 81%, 95% CI 67-92; positive predictive value 74.4%, negative predictive value 98.6%) using a model based on five other peptide and protein peaks (range 2.189-7.457 m/z) in luteal phase samples. The peak with the highest intensity (2.189 m/z) was identified as a fibrinogen β-chain peptide. Ultrasonography-negative endometriosis was best predicted (sensitivity 88%, 95% CI 73-100; specificity 84%, 95% CI 71-96) using a model based on five peptide peaks (range 2.058-42.065 m/z) in menstrual phase samples.

CONCLUSION:

A noninvasive test using proteomic analysis of plasma samples obtained during the menstrual phase enabled the diagnosis of endometriosis undetectable by ultrasonography with high sensitivity and specificity.

LEVEL OF EVIDENCE:

II.

Ann Thorac Surg. 2012 Feb;93(2):696-7.

Pleural endometriosis and recurrent pneumothorax: the role of magnetic resonance imaging.

Marchiori E, Zanetti G, Rafful PP, Hochhegger B.

Source

Department of Radiology, Federal University of Rio de Janeiro, Rua Thomaz Cameron, 438. Valparaiso. CEP 25685.120., Petrópolis, Rio de Janeiro, Brazil.

Acta Obstet Gynecol Scand. 2012 Jan 24. doi: 10.1111/j.1600-0412.2012.01367.x. [Epub ahead of print]

Diagnosis and treatment of rectovaginal endometriosis: An overview.

Kruse C, Seyer-Hansen M, Forman A.

Source

Department of Obstetrics and Gynecology, Aarhus University Hospital Skejby, Denmark.

Abstract

Rectovaginal endometriosis can be a cause of severe pain, dyspareunia and intestinal problems. A thorough examination is needed and should include diagnostic imaging, such as transvaginal or transrectal ultrasound or magnetic resonance imaging. Medical therapies such as oral contraceptives, progestins and levonorgestrel-releasing intrauterine devices all seem to reduce pain and should always be considered. Surgical treatment is challenging and implies a risk of severe complications. Endometriotic lesions with superficial affection of the rectal wall are preferably treated with local laparoscopic excision, while segmental rectal resection is needed in case of severe intestinal infiltration.This review describes available diagnostic tools, the possibilities for medical treatment and the alternative surgical approaches.

Acta Obstet Gynecol Scand. 2012 Jan 24. doi: 10.1111/j.1600-0412.2012.01366.x. [Epub ahead of print]

Continuous low-dose oral contraceptive in the treatment of colorectal endometriosis evaluated by rectal endoscopic ultrasonography.

Ferrari S, Persico P, DI Puppo F, Vigano’ P, Tandoi I, Garavaglia E, Giardina P, Mezzi G, Candiani M.

Source

Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milan, Università Vita-Salute San Raffaele, Milan, and Department of Gastroenterology and Gastrointestinal Endoscopy, San Raffaele Scientific Institute, Milan, Italy.

Abstract

Objective. Limited attention has been focused on the medical treatment of bowel endometriosis. This study evaluates the efficacy of a continuous low-dose oral contraceptive administration in treating pain and other symptoms associated with colorectal endometriotic nodules, as evaluated by rectal endoscopic ultrasonography. Design. Prospective observational study. Setting. Academic Department of San Raffaele Scientific Institute, Obstetrics and Gynecology Unit. Population. Symptomatic women in reproductive age (n=26) with colorectal nodules infiltrating at least the bowel muscularis propria and without a stenosis >50%. In 31% of the cases, endoscopic ultrasonography allowed to diagnose nodules located at more than 10 cm from the anal rim. Methods. Patients received a continuous low-dose oral contraceptive containing 15 μg ethinyl-estradiol and 60 μg gestodene for 12 months. Subjective symptoms were prospectively evaluated and nodule volumes were monitored using endoscopic ultrasonography. Results. A significant improvement in the intensity of all the considered symptoms (dysmenorrhea, non-menstrual pelvic pain, deep dyspareunia, and painful defecation) was seen when evaluated by a visual analog scale. A reduction in terms of both diameter (mean reduction 26%) and volume (mean reduction 62%) of the nodules was observed after a 12-month period. Conclusions. A continuous low-dose oral contraceptive therapy may reduce bowel endometriosis-associated symptoms. In addition, this therapy induces a significant volumetric reduction of colorectal plaques when evaluated by endoscopic ultrasonography.

Clin Exp Obstet Gynecol. 2011;38(4):394-8.

Frequency of ovarian endometriosis in epithelial ovarian cancer patients.

Dzatic-Smiljkovic O, Vasiljevic M, Djukic M, Vugdelic R, Vugdelic J.

Source

University of Belgrade, School of Medicine, Clinic of Gynaecology and Obstetrics Narodni Front, Belgrade, Serbia.

Abstract

PURPOSE:

The aim of this study was to determine the frequency of endometriosis in epithelial ovarian cancer patients.

METHODS:

Patients who had undergone epithelial ovarian cancer surgery between 2000 and 2004 were subjected to a retrospective analysis. The analysis focused on the presence of ovarian endometriosis, histological types and stages of ovarian cancer, treatment types and five-year survival rate.

RESULTS:

Out of the 210 operated ovarian cancer patients, 23 had coexisting ovarian endometriosis. Ovarian endometriosis was detected in 3.5% (4 of 113 patients) of cases with serous ovarian cancer, in 31.6% (12 of 38 patients) of cases with endometrioid, and in 36.8% (7 of 19 patients) of cases with clear cell ovarian cancer. The treatment of ovarian cancer patients was a combination of surgery and chemotherapy.

CONCLUSION:

Endometriosis was most frequently present in patients with clear cell (36.8%) and endometrioid ovarian cancers (31.6%). The five-year survival rate for ovarian cancer patients in all stages was 39.1%.

AJR Am J Roentgenol. 2012 Feb;198(2):W146-51.

Subcutaneous abdominal wall masses: radiological reasoning.

Stein L, Elsayes KM, Wagner-Bartak N.

Source

Department of Radiology, University of Michigan Health System, Ann Arbor, MI.

Abstract

OBJECTIVE: A 36-year-old woman presented to her primary care physician with right lower abdominal pain. Her physician subsequently requested a CT to rule out appendicitis. Contrast-enhanced CT was performed and revealed no evidence of appendicitis but showed two subcutaneous ovoid soft-tissue masses anterior to the rectus sheath in the upper pelvis. Pelvic MRI confirmed the two masses, which showed mild enhancement. The objective of this article is to discuss a diagnostic approach to subcutaneous soft-tissue masses in the abdominal wall. Diagnosis was endometriosis of the abdominal wall. CONCLUSION: Integrating salient imaging findings with clinical history is crucial when approaching the diagnosis of subcutaneous soft-tissue masses. The diagnosis of endometriosis should be entertained when soft-tissue masses are seen in the distribution of a cesarean section scar in a woman of reproductive age. Pain, particularly with a cyclic pattern, is highly suggestive of endometriosis. If endometriosis is suspected on CT or ultrasound, MRI can be performed for further evaluation. Definitive diagnosis is made with biopsy. Because subcutaneous nodules are so amenable percutaneous biopsy, imaging features, although of interest, are somewhat ancillary to the diagnostic workup.

Reprod Sci. 2012 Jan 19. [Epub ahead of print]

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis.

Cakmak H, Basar M, Seval-Celik Y, Osteen KG, Duleba AJ, Taylor HS, Lockwood CJ, Arici A.

Abstract

Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.

Mol Hum Reprod. 2012 Jan 20. [Epub ahead of print]

Apolipoprotein E Polymorphisms and Spontaneous Pregnancy Loss in Patients with Endometriosis.

Collazo MS, Porrata-Doria T, Flores I, Acevedo SF.

Source

Department of Physiology, Pharmacology, and Toxicology, Ponce School of Medicine and Health Sciences, Ponce, Puerto Rico.

Abstract

Endometriosis affects >10% of women during their reproductive years, many of whom report high rates of spontaneous pregnancy loss (SPL). We examined whether gene polymorphisms in apolipoprotein E (APOE), which is involved in lipoprotein metabolism, are associated with endometriosis and/or endometriosis-associated infertility. We conducted a cross-sectional genetic association study of women surgically confirmed to have endometriosis (n = 345) and no surgical evidence of the disease (n = 266). Genotyping of APOE polymorphism (ε2, ε3, ε4) was conducted by PCR-RFLP followed by visualization of specific patterns by gel electrophoresis. Statistical significance of differences in genotype and allelic frequencies was assessed using Pearson’s chi-square test and Risk analysis. Overall, we found no association between APOE genotype and diagnosis of endometriosis. However, patients with endometriosis who reported at least one SPL were 3 times more likely to be ε2 carriers and 2-fold less likely to be ε4 carriers. Compared to ε3 carriers, patients with endometriosis who were ε2 carriers and had at least one live birth reported 4 times the rate of SPL, while ε4 carriers were <0.4-fold less likely to report an SPL. Our data suggests that there may be an association between APOE allelic frequency and SPL in patients with endometriosis, which appears to be independent of mechanisms associated to infertility, an intriguing observation that deserves further investigation.

J Minim Invasive Gynecol. 2012 Jan 19. [Epub ahead of print]

Endometriosis after Laparoscopic Supracervical Hysterectomy with Uterine Morcellation: A Case Control Study.

Schuster MW, Wheeler TL 2nd, Richter HE.

Source

Ob-Gyn Associates, Decatur, AL.

Abstract

STUDY OBJECTIVE:

To compare the incidence of new-onset endometriosis after laparoscopic supracervical hysterectomy (LSH) with uterine morcellation to traditional routes.

DESIGN:

Single center case-control study (Canadian Task Force classification II-2) of hysterectomies performed from January 2006 through December 2008.

PATIENTS:

Two hundred seventy-seven laparoscopic supracervical hysterectomies with morcellation (cases) and 187 transvaginal or abdominal hysterectomies without morcellation (controls) were performed from January 2006 through December 2008.

INTERVENTIONS:

A total of 464 women underwent hysterectomy, 277 cases via laparoscopic supracervical approach (LSH) with morcellation and 187 performed either transvaginally or abdominally without morcellation. Repeat operative procedures were performed for other benign indications on 16 of 464 (3.5%) patients who had undergone prior hysterectomy.

MEASUREMENTS AND MAIN RESULTS:

One hundred two patients had endometriosis at the time of hysterectomy diagnosed by pathologic evaluation or gross visualization. In those without endometriosis, repeat operative procedures were performed for pain and bleeding in 3.3% (12/362). Sixty percent (3/5) of patients treated with LSH and 28.6% (2/7) of the control group were found to have newly diagnosed endometriosis, conferring a rate of 1.4% (3/217) in the LSH group and 1.4% (2/145) in the control subjects. In patients with endometriosis, repeat operative procedures for pain or bleeding occurred in 2.9% (3/102): 3/60 patients treated with LSH and none in the control group (0/42). Two of these 3 patients undergoing a second surgery had recurrent/continued endometriosis.

CONCLUSION:

Newly diagnosed endometriosis was noted in 1.4% of patients after hysterectomy, with a similar incidence between the LSH and control groups. Reoperation for those with endometriosis at the time of LSH with morcellation was infrequent, but endometriosis was usually found. Further research is needed to delineate risk factors for development of de novo endometriosis after hysterectomy.

Fertil Steril. 2012 Jan 19. [Epub ahead of print]

Chemokine CCL2 enhances survival and invasiveness of endometrial stromal cells in an autocrine manner by activating Akt and MAPK/Erk1/2 signal pathway.

Li MQ, Li HP, Meng YH, Wang XQ, Zhu XY, Mei J, Li DJ.

Source

Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics & Gynecology, Fudan University Shanghai Medical College, Shanghai, People’s Republic of China.

Abstract

OBJECTIVE:

To clarify the role and mechanism of CCL2 in regulating the biological functions of endometrial stromal cells (ESCs).

DESIGN:

The CCL2 effect on the viability, proliferation, and invasion in the eutopic ESCs from endometriosis.

SETTING:

Research laboratories.

PATIENT(S):

Patients with endometriosis aged 23-47 years.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Signal transduction and downstream molecules from CCR2.

RESULT(S):

We have found that the secretion of CCL2 by the eutopic ESCs from endometriosis is higher than that of healthy ESCs without endometriosis. The CCL2 can enhance the viability, proliferation, and invasion of ESCs in a dosage and time-dependent manner. Anti-CCL2 neutralizing antibody and CCR2 antagonist can completely abolish the increase in viability, proliferation, and invasiveness of ESCs induced by CCL2. The CCL2 can increase the expression of proliferating cell nuclear antigen, survivin, and matrix metalloproteinase 2, and decrease the expression of tissue inhibitor of metalloproteinase 1 and 2, and promote the viability, proliferation and invasiveness of ESCs by activating Akt and MAPK/Erk1/2 signal pathway, but not p38 and JNK signal pathway.

CONCLUSION(S):

CCL2 might play an important role in regulating the functions of ESCs through Akt and MAPK/Erk1/2 signal pathway, and overexpression of CCL2 in ESCs and peritoneal fluid (PF) would lead to onset and development of endometriosis.

Cytokine. 2012 Jan 18. [Epub ahead of print]

The effect of formoterol on peritoneal VEGF levels in rats with endometriosis.

Yilmaz N, Ozaksit G, Keskin R, Tapisiz O, Mollamahmutoglu L, Uysal S, Astarci M, Ustun H, Mulazımoglu B.

Source

Dr. Zekai Tahir Burak Women’s Health Research and Education Hospital, Ankara, Turkey.

Abstract

AIM:

The aim of this study is to investigate the effect of formoterol (β2 adrenergic receptor agonist) on peritoneal VEGF levels in rats with endometriosis.

MATERIALS AND METHODS:

Experimental endometriosis was constituted with implantation of endometrial tissue. The implants were examined by second laparatomy and rats were divided randomly into four groups. One cc saline was applied ip to the control (C) group (n=8) daily, 22.5μg/kg/day ip formoterol was applied to the second (F) group (n=10) daily, 22.5μg/kg/day ip formoterol and 10mg/kg/day ip propranolol were applied to the third (FP) group (n=10) daily, 45μg/kg/day ip formoterol was applied to the fourth (FF) group (n=9). Before treatment and after 30days treatment period, peritoneal VEGF levels, the volumes and histopathological properties of the implants were evaluated.

RESULTS:

There were significant differences in between the peritoneal VEGF levels before and after treatment in group 2(F) and group 4(FF) (p(a): 0.01, 0.01 respectively). But there were no significant changes in between the volumes of implants before and after treatment among the groups (p>0.05). There were no significant differences among the groups in histopathological parameters (p>0.05).

CONCLUSION:

Formoterol treatment was seen to have no effect on the volumes and histopathological structure of endometriotic implants in our study. On the other hand, based on the group 2(F) and 4’s (FF) VEGF levels after the treatment, low dose or high dose formoterol may be effective with long term therapy. Formoterol may reduce the development of endometriosis.

Fertil Steril. 2012 Jan 20. [Epub ahead of print]

Adiponectin and leptin systems in human endometrium during window of implantation.

Dos Santos E, Serazin V, Morvan C, Torre A, Wainer R, de Mazancourt P, Dieudonné MN.

Source

Service de Biochimie et Biologie Moléculaire, UPRES-EA 2493, UFR de Paris Ile de France Ouest, PRES Universud Paris, Centre Hospitalier de Poissy-Saint Germain, Poissy Cedex, France.

Abstract

OBJECTIVE:

To measure the expression of adiponectin, leptin, and their respective receptors in the human endometria of fertile women compared with women with unexplained recurrent implantation failure (IF) during the window of implantation.

DESIGN:

Controlled, prospective, clinical study.

SETTING:

Teaching hospital and university research laboratory.

PATIENT(S):

Thirty-one endometrial biopsies from women with IF and 19 fertile controls.

INTERVENTION(S):

Human endometrial biopsies.

MAIN OUTCOME MEASURE(S):

Gene and protein expression of endometrial biopsies.

RESULT(S):

Endometrial leptin expression was significantly lower in the IF group compared with fertile women. In contrast, leptin receptor (Ob-R) expression was higher in endometria of women with IF. Concerning the adiponectin system, adiponectin was expressed to the same extent in both groups. Conversely, the expression of its two receptors, AdipoR1 and AdipoR2, was reduced in endometria of women with IF compared with fertile women.

CONCLUSION(S):

Although progesterone resistance seems to be a common state of the endometrium in some human reproductive disorders, such as endometriosis or polycystic ovary syndrome, modification in leptin endometrial expression seems to be specific to IF. These results strongly suggest that changes in Ob-R and AdipoR expression profiles [1] should be implicated in the development of uterine receptivity, and [2] may therefore be potential new targets for prediction of IF.

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

Does colorectal endometriosis alter intestinal functions? A prospective manometric and questionnaire-based study.

Mabrouk M, Ferrini G, Montanari G, Di Donato N, Raimondo D, Stanghellini V, Corinaldesi R, Seracchioli R.

Source

Minimally Invasive Gynaecological Surgery Unit, S. Orsola Hospital, University of Bologna, Italy; Department of Obstetrics and Gynecology, Alexandria University, Egypt.

Abstract

OBJECTIVE:

To objectively evaluate using anorectal manometry whether endometriotic nodules influence intestinal function and to reveal subjective intestinal dysfunctions in patients with rectosigmoid deep infiltrating endometriosis.

DESIGN:

Prospective study.

SETTING:

Tertiary care university hospital.

PATIENT(S):

Patients (n = 25) with a preoperative diagnosis of rectosigmoid endometriosis.

INTERVENTION(S):

Patients underwent anorectal manometry; after that, they filled a questionnaire about defecatory functions and ranked their pain symptoms.

MAIN OUTCOME MEASURE(S):

The parameters studied were resting pressure, maximum squeezing pressure, pushing, rectoanal inhibitory reflex, and rectal sensibility. We analyzed the responses to the defecatory function questionnaire and the scored the endometriosis pain symptoms using a Visual Analogue Scale.

RESULT(S):

No alterations of the rectoanal inhibitory reflex were found. Hypertone of the internal anal sphincter was found in 20 of 25 patients. Almost half of the patients had an increase of the threshold of desire to defecate, and 7 patients had a reduction of the anal sphincter squeeze pressure. According to the responses to the defecatory function questionnaire, incomplete evacuation was the most common symptom.

CONCLUSION(S):

We did not find marked motility or sensitive dysfunctions at the anorectal manometry, whereas subjectively patients reported some defecatory disorders. We revealed the presence of hypertone of the internal anal sphincter in most of the patients. CLINICAL

TRIAL REGISTRATION NUMBER:

74/2010/O/Sper.

J Clin Endocrinol Metab. 2012 Jan 18. [Epub ahead of print]

Kruppel-Like Factor 9 and Progesterone Receptor Coregulation of Decidualizing Endometrial Stromal Cells: Implications for the Pathogenesis of Endometriosis.

Pabona JM, Simmen FA, Nikiforov MA, Zhuang D, Shankar K, Velarde MC, Zelenko Z, Giudice LC, Simmen RC.

Source

Departments of Physiology and Biophysics (J.M.P.P., F.A.S., R.C.M.S.) and Pediatrics (K.S.), University of Arkansas for Medical Sciences and Arkansas Children’s Nutrition Center (K.S., R.C.M.S.), Little Rock, Arkansas 72202; Department of Cell Stress Biology (M.A.N., D.Z.), Roswell Park Cancer Institute, Buffalo, New York 14263; and Department of Obstetrics, Gynecology and Reproductive Sciences (M.C.V., Z.Z., L.C.G.), University of California San Francisco, San Francisco, California 94143.

Abstract

Context:Endometriosis is characterized by progesterone resistance and associated with infertility. Krüppel-like factor 9 (KLF9) is a progesterone receptor (PGR)-interacting protein, and mice null for Klf9 are subfertile. Whether loss of KLF9 expression contributes to progesterone resistance of eutopic endometrium of women with endometriosis is unknown.Objective:The aims were to investigate 1) KLF9 expression in eutopic endometrium of women with and without endometriosis, 2) effects of attenuated KLF9 expression on WNT-signaling component expression and on WNT inhibitor Dickkopf-1 promoter activity in human endometrial stromal cells (HESC), and 3) PGR and KLF9 coregulation of the stromal transcriptome network.Methods:Transcript levels of KLF9, PGR, and WNT signaling components were measured in eutopic endometrium of women with and without endometriosis. Transcript and protein levels of WNT signaling components in HESC transfected with KLF9 and/or PGR small interfering RNA were analyzed by quantitative RT-PCR and Western blot. KLF9 and PGR coregulation of Dickkopf-1 promoter activity was evaluated using human Dickkopf-1-luciferase promoter/reporter constructs and by chromatin immunoprecipitation. KLF9 and PGR signaling networks were analyzed by gene expression array profiling.Results:Eutopic endometrium from women with endometriosis had reduced expression of KLF9 mRNA together with those of PGR-B, WNT4, WNT2, and DKK1. KLF9 and PGR were recruited to the DKK1 promoter and modified each other’s transactivity. In HESC, KLF9 and PGR coregulated components of the WNT, cytokine, and IGF gene networks that are implicated in endometriosis and infertility.Conclusion:Loss of KLF9 coregulation of endometrial stromal PGR-responsive gene networks may underlie progesterone resistance in endometriosis.

Cochrane Database Syst Rev. 2012 Jan 18;1:CD007677.

Pentoxifylline for endometriosis.

Lu D, Song H, Li Y, Clarke J, Shi G.

Source

Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, 3rd Section of Ren Min Nan Road, Chengdu, Sichuan, China, 610041.

Abstract

BACKGROUND:

Endometriosis is a chronic, recurring condition that occurs during the reproductive years. It is characterized by endometrial tissue developing outside the uterine cavity. This endometrial tissue development is dependent on oestrogen produced primarily by the ovaries and, therefore, traditional management has focused on ovarian suppression. In this review we considered the role of modulation of the immune system as an alternative approach. This is an update of a Cochrane Review previously published in 2009 (Lu 2009).

OBJECTIVES:

To assess the effects of pentoxifylline, which has anti-inflammatory effects, in subfertile, premenopausal women for the management of endometriosis.

SEARCH METHODS:

For the first publication of this review we searched the following databases (from inception to December 2008) for trials: Cochrane Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE, CINAHL, and PsycINFO. In addition, all reference lists of included trials were searched and experts in the field were contacted in an attempt to locate trials. This search was rerun to 23 November 2011, for this update.

SELECTION CRITERIA:

Randomised controlled trials (RCTs) comparing pentoxifylline with placebo or no treatment, medical treatment, or surgery in subfertile, premenopausal women were included.

DATA COLLECTION AND ANALYSIS:

Two review authors independently selected trials for inclusion, assessed trial risk of bias, and extracted data using data extraction forms. We contacted study authors for additional information and data. The domains assessed for risk of bias were sequence generation, allocation concealment, blinding, incomplete outcome data, and selective outcome reporting. Peto odds ratios (OR) were used for reporting dichotomous data with 95% confidence intervals (CI), whilst mean differences (MD) were expressed for continuous data. Statistical heterogeneity was assessed using the I(2) statistic.

MAIN RESULTS:

Four trials involving 334 participants were included. One RCT [n=34] showed pentoxifylline had no significant effect on reduction in pain (MD -1.60, 95% CI -3.32 to 0.12). There was no evidence of an increase in clinical pregnancy events in the pentoxifylline group compared with placebo (three RCTs [n=67] OR 1.54, 95% CI 0.89 to 266). One RCT studied recurrence of endometriosis [n=88] (OR 0.88,95% CI 0.27 to 2.84). No trials reported the effects of pentoxifylline on the odds of live birth rate per woman, improvement of endometriosis-related symptoms, or adverse events.

AUTHORS’ CONCLUSIONS:

This review has been updated in 2011. The results of the original review published in 2009 remain unchanged. There is still not enough evidence to support the use of pentoxifylline in the management of premenopausal women with endometriosis in terms of subfertility and relief of pain outcomes.

Update of

Arch Gynecol Obstet. 2012 Jan 19. [Epub ahead of print]

p53 codon 72 polymorphism and endometriosis: a meta-analysis.

Jia S, Xu L, Chan Y, Wu X, Yang S, Yu H, Yang H, Luo Y, Tang W.

Source

Laboratory of Molecular Genetics of Aging and Tumor, Faculty of Life Science and Technology, Kunming University of Science and Technology, Chenggong Campus, 727 South Jingming Road, Kunming, 650500, Yunnan, China.

Abstract

BACKGROUND:

p53 tumour suppressor gene Arg72Pro polymorphism has been associated with endometriosis. However, the current available data were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and endometriosis.

METHODS:

Electronic screening of PubMed library was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association.

RESULTS:

Six published studies, including 749 endometriosis and 857 controls were identified. The overall results suggested that the variant genotypes were not associated with the endometriosis risk (Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 1.552, 95% CI 0.916-2.632, p = 0.103). In the stratified analysis, individuals carried the Pro allele in a dominant model had increased risk of endometriosis (OR = 2.595, 95% CI 1.005-6.702, p = 0.049) in Asian subjects. The symmetric funnel plot, the Egger’s test (p = 0.602), and the Begg’s test (p = 0.167) were all suggestive of the lack of publication bias. However, the association was not significant between this polymorphism and endometriosis in Caucasian (OR = 1.005, 95% CI 0.755-1.337, p = 0.972).

CONCLUSION:

This meta-analysis suggests that p53 codon 72 Pro/Pro + Arg/Pro genotypes are associated with increased risk of endometriosis in Asian. To validate the association between p53 codon 72 polymorphism and endometriosis, further studies with larger participants worldwide are needed.

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