Int J Mol Med. 2011 Jan;27(1):87-94. doi: 10.3892/ijmm.2010.552. Epub 2010 Nov 8.

Inhibitory effect of curcumin on angiogenesis in ectopic endometrium of rats with experimental endometriosis.

Zhang Y, Cao H, Hu YY, Wang H, Zhang CJ.

Reproductive Medical Center, The Affiliated People’s Hospital of Hubei Medical University, Shiyan 442000, Hubei, P.R. China.

The aim of this study was to observe the inhibitory effect of curcumin on endometriosis (EMS) and to determine its influence on vascular endothelial growth factor (VEGF) and microvessel density (MVD) in eutopic and ectopic endometrium of experimental rats, thus exploring the pathogenesis of EMS offering more experimental evidence for the clinical use of curcumin. Forty-eight female virgin rats were subjected to autotransplantation of endometrium during the estrus stage. After four weeks, 8 rats were randomly sacrificed to confirm that the rat model was successful. The remaining rats were randomly divided into four groups. Three groups were intragastrically administered curcumin (50, 100 and 150 mg/kg), and the model group was intragastrically administered vehicle alone. All rats were treated daily for four continuous weeks and examined by histology and immunohistochemical staining for MVD of eutopic and ectopic endometrium. Our results revealed that the cubic capacity of focal tissue in gross appearance was high in the model group and dose-dependently diminished after treatment with curcumin (P<0.05). There was an increase in MVD and VEGF in the ectopic endometrium, which was decreased significantly after treatment with curcumin (P<0.05); the effects being dose-dependent. The correlation between MVD and VEGF was positive. In conclusion, heterogeneity was found to exist between eutopic and ectopic endometrium due to differences noted in MVD and the expression of VEGF between the eutopic and ectopic endometrium in the model group. Curcumin decreased the quantity of microvessels and VEGF protein expression in the heterotopic endometrium of rats with EMS.

Abdom Imaging. 2010 Dec;35(6):726-31.

Deep rectosigmoid endometriosis: “mushroom cap” sign on T2-weighted MR imaging.

Yoon JH, Choi D, Jang KT, Kim CK, Kim H, Lee SJ, Chun HK, Lee WY, Yun SH.

Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam-Ku, Seoul, Korea.

PURPOSE: The purpose of this study is to evaluate the “mushroom cap” sign on T2-weighted MR imaging in patients with submucosal tumors in the rectosigmoid colon.

METHODS: From January 2001 to August 2009, 12 patients with four different diseases presenting or mimicking submucosal tumors in the rectosigmoid colon underwent colonic resection. All patients with deep endometriosis (n = 6), gastrointestinal stromal tumor (n = 4), metastasis from ovary cancer (n = 1), and carcinoid tumor (n = 1) had either an MRI of the rectum or pelvis before surgery. We evaluated the MRI findings and compared them with the macroscopic and microscopic observations in the resected specimens.

RESULTS: In all six cases of deep endometriosis, a characteristic “mushroom cap” shaped appearance was found on T2-weighted MR imaging. Heterogeneous low signal intensity of the hypertrophic muscularis propria, covered with high signal intensity of the mucosa and submucosa on T2-weighted MR images, looked like a “mushroom cap” with the pattern of intraluminal endophytic growth. In histological findings, deep endometriosis involved the submucosa (n = 4) or mucosa (n = 2). The “mushroom cap” sign was not present in any of the six other tumors.

CONCLUSION: The “mushroom cap” sign on T2-weighted MR imaging may be a characteristic sign for diagnosing deep rectosigmoid endometriosis.

Abdom Imaging. 2010 Dec;35(6):708-15.

Deep pelvic endometriosis: MR imaging.

Marcal L, Nothaft MA, Coelho F, Choi H.

Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, USA.

OBJECTIVE: The purpose of the pictorial essay is to show the MR imaging (MRI) findings associated with deep pelvic endometriosis. CONCLUSION: MRI is an excellent imaging modality for the evaluation of patients with deep pelvic endometriosis, showing high accuracy in the diagnosis and prediction of disease extent. Its multiplanar capabilities and superior soft tissue contrast are extremely useful in the detection of deeply infiltrating endometriotic implants, even in the setting of intense desmoplastic response that may result in complete obliteration of the posterior cul-de-sac and fixed retroversion of the uterus, which limits the scope of laparoscopy. The use of endovaginal and rectal contrast is helpful to better delineate the anatomy of interest and map out the extent of disease, contributing to more effective treatment planning.

Abdom Imaging. 2010 Dec;35(6):732-6.

Preoperative assessment of intestinal endometriosis: A comparison of transvaginal sonography with water-contrast in the rectum, transrectal sonography, and barium enema.

Bergamini V, Ghezzi F, Scarperi S, Raffaelli R, Cromi A, Franchi M.

Department of Obstetrics and Gynecology, University of Verona, Italy.

To evaluate the accuracy of Transrectal Sonography (TRS) and a new technique, Transvaginal Sonography with Water-Contrast in the Rectum (RWC-TVS), in the diagnosis of rectosigmoid endometriosis, and the accuracy of Barium Enema (BE) and RWC-TVS in the detection of intestinal stenosis due to endometriosis. In a prospective study, we compared the findings of TRS and RWC-TVS performed before surgery with the operative and pathologic findings in 61 consecutive patients who underwent laparoscopy or laparotomy for suspected rectosigmoid endometriosis. The accuracy of BE and RWC-TVS in the detection of intestinal stenosis was evaluated comparing the radiologic and ultrasonographic results with the macroscopic findings at surgery and pathology. RWC-TVS diagnosed rectosigmoid endometriosis with the same accuracy of TRS and was equally efficient as BE in the detection of a significant intestinal lumen stenosis. For the diagnosis of rectosigmoid endometriosis the sensitivity, specificity, positive and negative predictive values of TRS and RWC-TVS were 88.2% and 96%, 80%, and 90%, 95.7%, and 98%, and 57.1% and 81.8%, respectively. For the detection of intestinal stenosis the sensitivity, specificity, positive and negative predictive values of BE and RWC-TVS were 93.7% and 87.5%, 94.2% and 91.4%, 88.2% and 82.3%, and 97% and 94.1%, respectively. RWC-TVS is a new, simple technique for a single-step and accurate preoperative assessment of rectosigmoid endometriosis.

Abdom Imaging. 2010 Dec;35(6):737-41.

Nuck canal endometriosis: MR imaging findings and clinical features.

Gaeta M, Minutoli F, Mileto A, Racchiusa S, Donato R, Bottari A, Blandino A.

Department of Radiological Sciences, Policlinico “G.Martino”, Messina, Italy.

OBJECTIVE: The purpose of this study was to describe the MR imaging findings of Nuck canal endometriosis (NCE).

MATERIALS AND METHODS: In a 10-year period, 486 out of 612 patients, with laparoscopically and/or surgically proven diagnosis of pelvic endometriosis, underwent MR imaging examination. The examinations were reviewed by two urogenital experienced radiologists working in consensus. Data analysis included: lesions location, size, morphological and signal intensity pattern, involvement of the adjacent muscles, and tendons.

RESULTS: In 372 out of 486 patients an MRI diagnosis of endometriosis was made. NCE was found in eight patients. All the lesions were located on the right side. The mean size of the lesions was 2.5 cm (range 1.5-4.5 cm). Two patterns of NCE were found: type 1, prevalently cystic (n = 2); and type 2, prevalently solid with small scattered cysts within lesion (n = 6). In all the patients, hemorrhagic hyperintense cysts could be seen on T1-weighted images. In four patients, the lesions involved the inguinal canal, and in another four patients, the lesions were only outside the inguinal canal. Involvement of the abdominis rectus muscle was seen in two patients, and of the adductor common tendon in two patients.

CONCLUSION: MR imaging permits the diagnosis of NCE as well as the evaluation of exact extension of the disease.

Abdom Imaging. 2010 Dec;35(6):742-9.

Anterior pelvic endometriosis: MRI features.

Novellas S, Chassang M, Bouaziz J, Delotte J, Toullalan O, Chevallier EP.

Centre Hospitalier Régional et Universitaire de Nice, Hôpital Archet, France.

Many atypical locations for deep endometriosis exist that are not well known to both the radiologist and gynecologist. This work explores these unusual localizations, which we have arbitrarily grouped under the term “anterior endometriosis” in contrast to the more common posterior presentation of deep endometriosis that has been so well described in the literature. Parietal and inguinal involvement is first detailed, followed by a description of deep endometriosis involving the urinary system and anterior supporting ligaments of the uterus. A necessary adaptation to the MRI protocol in order to accurately diagnosis deep anterior endometriosis as well as specific diagnostic criteria for each type of lesion is reviewed.

Abdom Imaging. 2010 Dec;35(6):716-25.

Diagnosis of deep infiltrating endometriosis: accuracy of magnetic resonance imaging and transvaginal 3D ultrasonography.

Grasso RF, Di Giacomo V, Sedati P, Sizzi O, Florio G, Faiella E, Rossetti A, Del Vescovo R, Zobel BB.

Department of Diagnostic Imaging, University of Rome, Italy.

PURPOSE: To compare two different imaging modalities, magnetic resonance (MR), and three-dimensional sonography (3DUS), in order to evaluate the specific role in preoperative work-up of deep infiltrating endometriosis.

MATERIALS AND METHODS: 33 women with endometriosis underwent 3DUS and MR followed by surgical and histopathological investigations. Investigators described the disease extension in the following sites: torus uterinus and uterosacral ligaments (USL), vagina, rectovaginal-septum, rectosigmoid, bladder, ovaries. Results were compared with surgical and histopathological findings.

RESULTS: Ovarian and deep pelvic endometriosis were found by surgery and histology in, respectively, 24 (72.7%) and 22 (66.6%) of the 33 patients. Sensitivity and specificity values of 3DUS for the diagnosis of endometrial cysts were 87.5% and 100%, respectively; those of MRI were 96.8% and 91.1%, respectively. Sensitivity and specificity of 3DUS for the diagnosis of deep infiltrating endometriosis in specific sites were: USL 50% and 94.7%; vagina 84% and 80%; rectovaginal-septum 76.9% and 100%; rectosigmoid 33.3% and 100%; bladder 25% and 100%. Those of MR were: USL 69.2% and 94.3%; vagina 83.3% and 88.8%; rectovaginal-septum 76.4% and 100%; restosigmoid 75% and 100%; bladder 83.3% and 100%.

CONCLUSIONS: MR accurately diagnoses deep infiltrating endometriosis; 3DUS accurately diagnoses deep infiltrating endometriosis in specific locations.

Am J Pathol. 2010 Dec;177(6):2963-70. Epub 2010 Nov 5.

Antiproliferative effects of cannabinoid agonists on deep infiltrating endometriosis.

Leconte M, Nicco C, Ngô C, Arkwright S, Chéreau C, Guibourdenche J, Weill B, Chapron C, Dousset B, Batteux F.

Laboratoire d’immunologie, Hôpital Cochin, 75679 Paris cedex 14.

Deep infiltrating endometriosis (DIE) is characterized by chronic pain, hyperproliferation of endometriotic cells and fibrosis. Since cannabinoids are endowed with antiproliferative and antifibrotic properties, in addition to their psychogenic and analgesic effects, cannabinoid agonists have been evaluated in DIE both in vitro and in vivo. The in vitro effects of the cannabinoid agonist WIN 55212-2 were evaluated on primary endometriotic and endometrial stromal and epithelial cell lines extracted from patients with or without DIE. Cell proliferation was determined by thymidine incorporation and production of reactive oxygen species by spectrofluorometry. ERK and Akt pathways were studied by immunoblotting. Immunoblotting of α-smooth muscle actin was studied as evidence of myofibroblastic transformation. The in vivo effects of WIN 55212-2 were evaluated on Nude mice implanted with human deep infiltrating endometriotic nodules. The in vitro treatment of stromal endometriotic cells by WIN 55212-2 decreased cell proliferation, reactive oxygen species production, and α-smooth muscle actin expression. The decrease in cell proliferation induced by WIN 55212-2 was not associated with a decrease in ERK activation, but was associated with the inhibition of Akt activation. WIN 55212-2 abrogated the growth of endometriotic tissue implanted in Nude mice. Cannabinoid agonists exert anti-proliferative effects on stromal endometriotic cells linked to the inhibition of the Akt pathway. These beneficial effects of cannabinoid agonists on DIE have been confirmed in vivo.

Clin Radiol. 2010 Dec;65(12):1031-7. Epub 2010 Sep 9.

Imaging malignant and apparent malignant transformation of benign gynaecological disease.

Lee AY, Poder L, Qayyum A, Wang ZJ, Yeh BM, Coakley FV.

Department of Radiology, University of California San Francisco, San Francisco, CA 94143-0628, USA.

Common benign gynaecological diseases, such as leiomyoma, adenomyosis, endometriosis, and mature teratoma, rarely undergo malignant transformation. Benign transformations that may mimic malignancy include benign metastasizing leiomyoma, massive ovarian oedema, decidualization of endometrioma, and rupture of mature teratoma. The aim of this review is to provide a contemporary overview of imaging findings in malignant and apparent malignant transformation of benign gynaecological disease.

Copyright © 2010 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Eur J Obstet Gynecol Reprod Biol. 2010 Dec;153(2):227-9. Epub 2010 Aug 21.

Deep rectal and parametrial infiltrating endometriosis with monolateral pudendal nerve involvement: case report and laparoscopic nerve-sparing approach.

Ceccaroni M, Clarizia R, Roviglione G, Bruni F, Ruffo G, Peters I, De Placido G, Minelli L.

Expert Opin Pharmacother. 2010 Dec;11(17):2929-32. Epub 2010 Oct 23.

Triptorelin embonate: a 6-month formulation for prostate cancer.

Whelan P.

University of Leeds, Leeds, UK.

IMPORTANCE OF THE FIELD: Luteinizing hormone releasing hormone (LH RH) agonists are the major agent for androgen deprivation therapy in advanced and metastatic prostate cancer. They also have a role in endometriosis, uterine fibroids and central precocious puberty. AREAS COVERED IN THE

REVIEW: Triptorelin embonate 22.5 mg is a new, sustained-release, 6-month formulation of an LH RH agonist. It possesses longer duration of action than the current standard 3-month preparation and appears to have similar efficacy and side effects.

WHAT THE READER WILL GAIN: The use of LH RH agonists for androgen deprivation in prostate cancer has increased considerably in the last 20 years. Recent work has shown that some of this usage has constituted overtreatment and it is within these newer paradigms of therapy that the new 6-month preparation is situated.

TAKE HOME MESSAGE: The new 6-month LH RH preparation – triptorelin embonate – will be of help in several key areas of therapy for prostate cancer, notably as an adjunct to radiation therapy and chemotherapy. It possesses a similar effect, but with fewer side effects, than those that are now commonly available.

Fertil Steril. 2010 Dec;94(7):2923-6. Epub 2010 Jun 17.

The vitamin E-binding protein afamin is altered significantly in the peritoneal fluid of women with endometriosis.

Seeber BE, Czech T, Buchner H, Barnhart KT, Seger C, Daxenbichler G, Wildt L, Dieplinger H.

Department of Gynecologic Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Innsbruck, Austria.

The objective of this case-control study of 242 reproductive-age women was to determine the concentration of afamin in the serum and peritoneal fluid of women with and without endometriosis and to test afamin as a diagnostic marker of endometriosis. Afamin levels were altered significantly in the peritoneal fluid of women with endometriosis compared with disease-free controls, correlated with vitamin E levels, and are consistent with increased oxidative stress in the peritoneal cavity of women with endometriosis.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2817-9. Epub 2010 Aug 1.

Loss of sympathetic nerve fibers in intestinal endometriosis.

Ferrero S, Haas S, Remorgida V, Camerini G, Fulcheri E, Ragni N, Straub RH, Capellino S.

Department of Obstetrics and Gynecology, San Martino Hospital and University of Genoa, Genoa, Italy.

This study analyzed by immunofluorescence staining the sympathetic innervation in the bowel adjacent to the endometriotic lesion and in the healthy tissue at the border of the resected specimen. Sympathetic nerve fibers are significantly reduced in the mucosal and muscular layer near the endometriotic lesions; in contrast, sensory nerve fiber density is not altered in the area near the endometriotic lesions.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2796-9. Epub 2010 Jul 21.

Use of oral contraceptives in women with endometriosis before assisted reproduction treatment improves outcomes.

de Ziegler D, Gayet V, Aubriot FX, Fauque P, Streuli I, Wolf JP, de Mouzon J, Chapron C.

Department of Obstetrics, Gynecology, and Reproductive Medicine, Université Paris Descartes-Assistance Publique Hôpitaux de Paris, CHU Cochin, Paris, France.

In women with endometriosis, including those with endometriomas, 6 to 8 weeks of continuous use of oral contraception (OC) before assisted reproduction treatment (ART) maintains ART outcomes comparable with the outcomes of age-matched controls without endometriosis. In contrast, ART outcomes are markedly compromised in endometriosis patients who are not pretreated with OC. Ovarian responsiveness to stimulation was not altered by 6 to 8 weeks’ use of pre-ART OC, including in poor responders with endometriomas.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2885-7. Epub 2010 Jul 23.

Endometrial expression of relaxin and relaxin receptor in endometriosis.

Morelli SS, Petraglia F, Weiss G, Luisi S, Florio P, Wojtczuk A, Goldsmith LT.

Department of Obstetrics, Gynecology and Women’s Health, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey.

Our studies demonstrate significantly lower expression of relaxin and its receptor in ectopic endometriotic tissues than their expression in eutopic endometrium and in endometrium from normal controls. These data suggest that in normal and eutopic endometrium, relaxin may exert a protective effect against endometriosis.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2905-8. Epub 2010 Jul 23.

More than antioxidant: N-acetyl-L-cysteine in a murine model of endometriosis.

Pittaluga E, Costa G, Krasnowska E, Brunelli R, Lundeberg T, Porpora MG, Santucci D, Parasassi T.

Institute of Neurobiology and Molecular Medicine, National Research Council, Rome, Italy.

N-acetyl-L-cysteine exerts a complex action on endometrial cells, involving regulation of gene expression and protein activity and location, all converging into a decreased proliferation and a switch toward a differentiating, less invasive, and less inflammatory phenotype. Also considering the lack of undesired side effects, including unaffected fertility potential, this suggests a beneficial use of NAC in endometriosis clinical treatment.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2860-2863.e3.

Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis.

Khan KN, Kitajima M, Hiraki K, Yamaguchi N, Katamine S, Matsuyama T, Nakashima M, Fujishita A, Ishimaru T, Masuzaki H.

Department of Obstetrics and Gynecology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

To test the hypothesis that bacterial contamination of menstrual blood could be a local biologic event in the development of endometriosis, menstrual blood was cultured and bacterial endotoxin was measured in menstrual blood and peritoneal fluid. Our results suggest that compared with control women, higher colony formation of Escherichia coli in menstrual blood and endotoxin levels in menstrual fluid and peritoneal fluid in women with endometriosis may promote Toll-like receptor 4-mediated growth of endometriosis.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2528-30.

Detection of mitochondrial biomarkers in eutopic endometria of endometriosis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.

Ding X, Wang L, Ren Y, Zheng W.

Department of Gynecology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China.

OBJECTIVES: To detect specific mitochondrial proteins in eutopic endometrial samples from women with and without endometriosis and to build diagnostic models.

DESIGN: Eutopic endometrial samples from women with endometriosis (excluding adenomyosis) and women with benign indications as control were studied by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry protein-chip technology. After finding the biomarkers, the diagnostic model was evaluated and validated by leave-one cross-validation.

SETTING: Collaborative investigation in an academic research environment.

PATIENT(S): Twenty-four patients with endometriosis (excluding adenomyosis) and 29 patients with benign indications as control.

INTERVENTION(S): Surgical excision of eutopic endometrial biopsy of patients with endometriosis and controls.

MAIN OUTCOME MEASURE(S): Mitochondrial protein expression.

RESULT(S): Seventy-eight qualified mitochondrial protein peaks were detected, ten of them had a significant difference. Three combined potential biomarkers, with mass-to-charge ratios (m/z) of 15,334, 15,128, and 16,069, were found, and the diagnostic system distinguished endometriosis from control samples with a specificity of 86.2% and a sensitivity of 87.5%.

CONCLUSION(S): We discovered potential mitochondrial biomarkers of eutopic endometrium in endometriosis and set up a diagnostic model. Further identification of the proteins we found will help to explain pathology, new diagnoses, and therapeutic approaches for endometriosis.

Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2838-42. Epub 2010 Jun 3.

Romidepsin reduces histone deacetylase activity, induces acetylation of histones, inhibits proliferation, and activates apoptosis in immortalized epithelial endometriotic cells.

Imesch P, Fink D, Fedier A.

Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.

Romidepsin inhibited HDAC activity, produced acetylation of the histone proteins, up-regulated p21, and down-regulated cyclins B1 and D1, resulting in proliferation inhibition and apoptosis activation in 11z immortalized epithelial endometriotic cells. Our findings provide evidence that endometriotic cells are sensitive to the epigenetic effects of romidepsin and suggest that endometriosis may be therapeutically targeted by romidepsin.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2942-4. Epub 2010 Jun 19.

Application of the nuclear factor-κB inhibitor pyrrolidine dithiocarbamate for the treatment of endometriosis: an in vitro study.

Zhang JJ, Xu ZM, Dai HY, Ji XQ, Duan YY, Zhang CM, Qin DY.

Department of Obstetrics and Gynecology, Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong, People’s Republic of China.

This study demonstrated that pyrrolidine dithiocarbamate (PDTC), a potent nuclear factor-κB inhibitor, showed stronger inhibitory effects on nuclear factor-κB activation in endometriotic stromal cells than in normal endometrial stromal cells as determined by electrophoretic mobility shift assay and Western blot analysis. Pretreatment of endometriotic stromal cells with PDTC attenuated tumor necrosis factor-α-induced expressions of CD44s, matrix metalloproteinase-9, and vascular endothelial growth factor whereas reversed tumor necrosis factor-α-reduced expressions of tissue inhibitor of metalloproteinase-1 revealed by reverse transcriptase polymerase chain reaction and Western blot analysis, suggesting that PDTC may represent a novel therapeutic strategy for treatment of endometriosis.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2531-5. Epub 2010 May 31.

Imatinib decreases endometrial stromal cell transmesothial migration and proliferation in the extracellular matrix of modeled peritoneum.

Griffith JS, Binkley PA, Kirma NB, Schenken RS, Witz CA, Tekmal RR.

Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Texas Health Science Center San Antonio, San Antonio, Texas.

OBJECTIVE: To characterize imatinib’s effect on endometrial stromal cell (ESC) attachment, proliferation, and invasion in modeled peritoneum.

DESIGN: In vitro study.

SETTING: Academic medical center.

PATIENT(S): Twelve normally cycling women.

INTERVENTION(S): Imatinib treatment in ESCs from women without endometriosis.

MAIN OUTCOME MEASURE(S): Rate of ESC attachment, proliferation, and invasion.

RESULT(S): Imatinib treatment at 10 μM had no effect on ESC attachment. Treatment with 0.5 μM, 2 μM, and 10 μM of imatinib reduced ESC proliferation by 30%, 72%, and 76%, respectively. The 0.1 μM dose of imatinib had no effect on proliferation. Treatment with 5 μM and 10 μM of imatinib reduced ESC invasion by 30% and 73%, respectively. The 2 μM dose had no effect on invasion.

CONCLUSION(S): Imatinib treatment reduces ESC proliferation and invasion in modeled peritoneum without altering attachment. Imatinib may have a therapeutic role in endometriosis treatment.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2758-60. Epub 2010 May 26.

Robotic versus standard laparoscopy for the treatment of endometriosis.

Nezhat C, Lewis M, Kotikela S, Veeraswamy A, Saadat L, Hajhosseini B, Nezhat C.

Center for Minimally Invasive and Robotic Surgery, Stanford University Medical Center, Palo Alto, California.

OBJECTIVE: To compare robot assisted laparoscopic platform to standard laparoscopy for the treatment of endometriosis.

DESIGN: A retrospective cohort controlled study.

SETTING: Tertiary referral center.

PATIENT(S): Seventy-eight reproductive aged women.

INTERVENTION(S): Robot assisted or standard laparoscopy for the treatment of endometriosis between January 2008 and January 2009.

MAIN OUTCOME MEASURE(S): Operative time, estimated blood loss, hospitalization time, intraoperative and postoperative complications.

RESULT(S): Seventy-eight patients underwent treatment of endometriosis, 40 by robot assisted laparoscopy and 38 by standard laparoscopy. The two groups were matched for age, body mass index (BMI), stage of endometriosis, and previous abdominal surgery. Mean operative time with the robot was 191 minutes (range 135-295 minutes) compared with 159 minutes (range 85-320 minutes) during standard laparoscopy. There were no significant differences in blood loss, hospitalization, intraoperative or postoperative complications. There were no conversions to laparotomy.

CONCLUSION(S): Both robot assisted laparoscopic and standard laparoscopic treatment of endometriosis have excellent outcomes. The robotic technique required significantly longer surgical and anesthesia time, as well as larger trocars.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2769.e1-4. Epub 2010 May 26.

Florid endometriosis in a postmenopausal woman.

Bailey AP, Schutt AK, Modesitt SC.

Department of Obstetrics and Gynecology, University of Virginia, Charlottesville, Virginia.

OBJECTIVE: To report a case of florid endometriosis.

DESIGN: Case report.

SETTING: University hospital.

PATIENT(S): A 53-year-old postmenopausal woman with a 10-cm retroperitoneal mass comprised of endometriosis causing hydroureteronephrosis and loss of ipsilateral kidney function.

INTERVENTION(S): The patient underwent exploratory laparotomy with extensive lysis of adhesions, right nephrectomy, radical resection of the retroperitoneal mass including partial resection of the psoas muscle, dissection from the inferior vena cava, and resection of distal ileum, cecum, and appendix with a primary ileoascending colon reanastomosis.

MAIN OUTCOME MEASURE(S): Postoperative symptom resolution.

RESULT(S): The patient had widespread adhesive disease with a primary retroperitoneal endometriotic mass and a secondary mass involving the small bowel mesentery. Endometriomas were found in the right kidney and right distal ureter. Additional endometriotic implants were found at the right common iliac bifurcation, appendix, and in multiple mesenteric nodules. No residual ovarian tissue was identified, and preoperative FSH and estrogen (E) levels indicated no evidence of an ovarian remnant.

CONCLUSION(S): Severe endometriosis caused ipsilateral renal failure despite postmenopausal levels of E and FSH, supporting the theory that endometriotic implants may have an autocrine function involving E biosynthesis or may respond to hormone production in adipose tissue.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2521-7. Epub 2010 Apr 28.

P(450)Arom induction in isolated control endometrial cells by peritoneal fluid from women with endometriosis.

Castro J, Torres M, Sovino H, Fuentes A, Boric MA, Johnson MC.

Institute of Maternal and Child Research, Faculty of Medicine, University of Chile, Santiago, Chile.

OBJECTIVE: To study the effect of peritoneal fluid from women with (PF-E) and without (PF-C) endometriosis on P(450)Arom expression in endometrial cells.

DESIGN: Experimental study.

SETTING: University research unit.

PATIENT(S): Forty women of reproductive age with (n = 22) or without (control; n = 18) endometriosis.

INTERVENTION(S): Peritoneal fluid and eutopic endometrial samples were obtained during surgery from women with (n = 13 and 9, respectively) and without (n = 4 and 14, respectively) endometriosis.

MAIN OUTCOME MEASURE(S): Expression study for P(450)Arom, steroid factor 1 (SF-1), chicken ovalbumin upstream transcription factor I (COUP-TFI), and COUP-TFII messenger RNA (reverse transcriptase-polymerase chain reacion) and/or protein (immunoblot) in isolated endometrial epithelial cells transfected or not with expression vector containing SF-1, COUP-TFI, or COUP-TFII complementary DNAs.

RESULT(S): Basal messenger RNA and/or protein expression of P(450)Arom and SF-1 were augmented in endometriosis, and that of COUP-TF was diminished. In control cells, (Bu)(2)cAMP and PF-E increased P(450)Arom and SF-1 expression (but not COUP-TF expression) in a dose-dependent way, an effect not observed with PF-C, adsorbed PF-E, or 10(-5) M indomethacin. Transfected cells confirmed these results. Any treatments modified the studied molecules in endometriosis cells.

CONCLUSION(S): These data indicate that molecules contained in PF-E favor an estrogenic microenvironment, suggesting a role in the etiopathogenesis of endometriosis enabling the survival, maintenance, and growth of endometrial implants in the ectopic locations.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2541-6. Epub 2010 Apr 22.

Possible roles of oxytocin receptor and vasopressin-1α receptor in the pathomechanism of dysperistalsis and dysmenorrhea in patients with adenomyosis uteri.

Mechsner S, Grum B, Gericke C, Loddenkemper C, Dudenhausen JW, Ebert AD.

Endometriosis Research Center, Department of Obstetrics and Gynecology, Campus Benjamin Franklin, Berlin, Germany.

OBJECTIVE: To investigate the expression of oxytocin (OTR) and/or vasopressin (VP1αR) receptor in patients with and without adenomyosis uteri.

DESIGN: Retrospective nonrandomized study.

SETTING: University hospital endometriosis research center.

PATIENT(S): Forty patients with histologically proven adenomyosis and 40 patients without adenomyosis who had undergone hysterectomy for dysmenorrhea, bleeding disorders, and fibroids.

INTERVENTION(S): Immunohistochemical examination of both OTR and VP1αR expression in endometrium, myometrium, and adenomyotic lesions, and identification of smooth muscle cells using antibodies against OTR, VP1αR, and smooth muscle actin (sm-actin).

MAIN OUTCOME MEASURE(S): The immunoreactive score (IRS) was used for expression of OTR, VP1αR, and sm-actin.

RESULT(S): Expression of OTR in epithelial cells of adenomyotic lesions and surrounding myometrial cells was detectable. VP1αR was expressed only in myometrial cells and blood vessels. Using a specific anti-sm-actin antibody, another spindle cell population was characterized to represent smooth muscle cells which are in direct contact with the adenomyotic stroma. Compared with the unaffected myometrium, the surrounding adenomyosis-associated myometrium overexpressed OTR and showed changes in morphology. In the uteri of patients with adenomyosis, the junctional zone was often seen to be quite fissured.

CONCLUSION(S): In addition to the specific expression of VP1αR, OTR expression and morphologic changes in the myometrial architecture of uteri having adenomyosis support the hypothesis that dysperistalsis plays an essential role in the development of endometriosis and dysmenorrhea. In the near future, specific inhibition of this receptor might yield a promising treatment for therapy.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2552-2557.e1. Epub 2010 Apr 18.

Serum anti-PDIK1L autoantibody as a novel marker for endometriosis.

Nabeta M, Abe Y, Haraguchi R, Kito K, Kusanagi Y, Ito M.

Department of Molecular Pathology, Ehime University Graduate School of Medicine, Ehime, Japan; Department of Obstetrics and Gynecology, Ehime University Graduate School of Medicine, Ehime, Japan.

OBJECTIVE: To establish a novel serum marker for endometriosis, serum autoantibodies (autoAbs) were investigated using a proteomic approach.

DESIGN: Retrospective study.

SETTING: Departments of Molecular Pathology and Obstetrics and Gynecology in Ehime University and University Hospital.

PATIENT(S): Sixty-nine patients with endometriosis, 38 disease control patients without endometriosis, and 44 healthy volunteers.

INTERVENTION(S): Autoantibodies in sera of endometriotic patients and healthy controls were investigated using a human fibroblast cell line, two-dimensional gel electrophoresis, and Western blotting. Proteins in reacted spots were identified using MALDI time of flight mass spectrometry with MASCOT analysis. ELISAs were established using recombinant proteins, and autoAb-titers were estimated in sera of endometriotic patients and controls.

MAIN OUTCOME MEASURE(S): Identification of serum autoAb useful for diagnosis of endometriosis.

RESULT(S): Several autoAbs were identified. ELISAs were established and serum autoAb titers were estimated. Among those identified, anti-PDIK1L-autoAb levels were significantly elevated in endometriotic patients. Sensitivity (59.4%) and accuracy (72.8%) of serum anti-PDIK1L-autoAb assay were better than those of serum CA125 levels (36.2% and 62.9%, respectively) in diagnosis of endometriosis. Additionally, anti-PDIK1L-autoAb could detect endometriotic patients in early stages.

CONCLUSION(S): Serum anti-PDIK1L-autoAb can be a new serum marker for the diagnosis of endometriosis. This study validates further clinical evaluation of this novel marker.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2558-63. Epub 2010 Apr 18.

Prokineticin 1, homeobox A10, and progesterone receptor messenger ribonucleic acid expression in primary cultures of endometrial stromal cells isolated from endometrium of healthy women and from eutopic endometrium of women with endometriosis.

Tiberi F, Tropea A, Romani F, Apa R, Marana R, Lanzone A.

Istituto Scientifico Internazionale “Paolo VI,” Università Cattolica del Sacro Cuore (UCSC), Rome, Italy.

OBJECTIVE: To examine prokineticin 1 (PROK1), homeobox (HOX) A10, and P receptor (PR) messenger ribonucleic acid (mRNA) expression in primary cultures of endometrial stromal cells (ESC) obtained from eutopic endometrial samples of patients with endometriosis and to clarify whether in vitro steroid hormone dependence of PROK1 gene expression is altered in endometriosis.

DESIGN: Prospective laboratory study.

SETTING: Tertiary university hospital.

PATIENT(S): Twelve normal women (controls) and 12 patients affected by moderate to severe endometriosis in the midsecretory phase of the menstrual cycle.

INTERVENTION(S): Endometrial specimens were obtained from control women and from women affected by endometriosis; ESC were isolated from endometrial biopsies, and primary cultures were established.

MAIN OUTCOME MEASURE(S): Real-time polymerase chain reaction analysis of PROK1, HOXA10, and PR mRNA expression in ESC after 1-4 days of steroid hormone treatment and after decidual differentiation.

RESULT(S): Contrary to ESC from control women, in ESC obtained from women affected by endometriosis PROK1 and PR mRNA expression was not induced by 1-4 days of treatment with steroid hormones. Nevertheless, when ESC from both groups of women were differentiated to decidual phenotype, PROK1 mRNA was up-regulated and PR and HOXA10 mRNA were down-regulated to the same extent.

CONCLUSION(S): Our results provide additional evidence for P resistance in endometriosis.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2536-40. Epub 2010 Mar 31.

Surgical treatment of endometriosis: a prospective randomized double-blinded trial comparing excision and ablation.

Healey M, Ang WC, Cheng C.

Royal Women’s Hospital, Melbourne, Victoria, Australia.

OBJECTIVE: To compare reduction of pain following laparoscopy after ablation or excision of endometriosis.

DESIGN: A prospective, randomized, double-blind study.

SETTING: Endometriosis and pelvic pain clinic at a university teaching hospital.

PATIENT(S): Women of reproductive age presenting with pelvic pain and visually proved endometriosis.

INTERVENTION(S): Subjects completed a questionnaire rating their various pains using visual analogue scales (VASs). After visual identification subjects were assigned randomly to treatment with ablation or excision by supervised training gynecologists as primary surgeon. Follow-up questionnaires at 3, 6, 9, and 12 months documented pain levels.

MAIN OUTCOME MEASURE(S): Change in overall pain VAS score at 12 months after operation.

RESULT(S): There was no significant difference in reduction in overall pain VAS scores at 12 months when comparing ablation and excision.

CONCLUSION(S): This study has not been able to demonstrate a significant difference in pain reduction between ablation and excisional treatments. Nonsignificant trends suggest that a larger study may find a difference in outcomes looking at dyspareunia or dyschezia.

Crown Copyright © 2010. Published by Elsevier Inc. All rights reserved.

Fertil Steril. 2010 Dec;94(7):2761-5. Epub 2010 Mar 31.

Diagnosis of endometriosis of the rectovaginal septum using introital three-dimensional ultrasonography.

Pascual MA, Guerriero S, Hereter L, Barri-Soldevila P, Ajossa S, Graupera B, Rodriguez I.

Department of Obstetrics, Gynecology, and Reproduction, Institut Universitari Dexeus, University of Barcelona, Barcelona, Spain.

OBJECTIVE: To evaluate the diagnostic accuracy of introital three-dimensional (3D) transvaginal sonography for preoperative detection of rectovaginal septal endometriosis.

DESIGN: Ultrasonographic results were compared with surgical and histologic findings.

SETTING: University Department of Obstetrics and Gynecology.

PATIENT(S): This prospective study included 39 women with suspected rectovaginal endometriosis.

INTERVENTION(S): All patients underwent 3D transvaginal sonography for the evaluation of the rectovaginal septum, before undergoing laparoscopic radical resection of endometriosis. Rectovaginal endometriosis was defined as hypoechoic areas, nodules, or anatomic distortion of this specific location.

MAIN OUTCOME MEASURE(S): Sensitivity, specificity, and likelihood ratios (positive or negative) were calculated with 95% confidence intervals (CIs).

RESULT(S): Surgery associated with histopathologic evaluation revealed deep endometriosis in the rectovaginal septum in 19 patients. The specificity, sensitivity, positive likelihood ratio, and negative likelihood ratio were 94.7% (95% CI, 78.6%-99.7%), 89.5% (95% CI, 73.3%-94.5%), 17.2 (95% CI, 2.51-115), and 0.11 (95% CI, 0.03-0.41), respectively.

CONCLUSION(S): Introital 3D ultrasonography seems to be an effective method for the diagnosis of endometriosis of the rectovaginal septum and should be included in the preoperative evaluation of patients with clinical suspicion of deep endometriosis.

Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Gynecol Endocrinol. 2010 Dec;26(12):851-4.

Hormonal contraceptives and endometriosis/adenomyosis.

Schindler AE.

Over the past 50 years hormonal contraceptives have gradually developed to be cost-effective medical treatment modalities for primary and secondary therapy of endometriosis/adenomyosis. This is particularly true for the various estrogen/progestogen combinations as monophasic – particularly progestogen-dominant – preparations in cyclic, long-cyclic and continuous treatment forms. An alternative is the progestogen-only therapy used continuously. Therapeutic effects have been shown for peritoneal, ovarian and deep-infiltrating endometriosis as well as for adenomyosis. An individualized, medical long-term treatment concept to control endometriosis/adenomyosis-related symptoms, endometriosis/adenomyosis development and minimizing the recurrence rate needs to be further studied in women, who do not desire to become pregnant.

Hum Reprod. 2010 Dec;25(12):3110-6. Epub 2010 Oct 17.

SB203580, a p38 mitogen-activated protein kinase inhibitor, suppresses the development of endometriosis by down-regulating proinflammatory cytokines and proteolytic factors in a mouse model.

Zhou WD, Yang HM, Wang Q, Su DY, Liu FA, Zhao M, Chen QH, Chen QX.

Key Laboratory of Ministry of Education for Cell Biology and Tumor Cell Engineering, School of Life Sciences, Xiamen University, Xiamen 361005, China.

BACKGROUND p38 mitogen-activated protein kinase (p38 MAPK), a regulator of inflammation, may play a role in the pathogenesis of endometriosis (EM). We studied the effect of SB203580, a p38 MAPK inhibitor, on the development of EM in a mouse model. METHODS EM was induced in BALB/c mice by peritoneal injection of endometrium-rich fragments. Mice (n = 15) were injected i.p. for 24 days with SB203580 and 15 mice served as positive controls (EM group). Sham-operated mice received carrier only. Peritoneal fluid (PF) cells were collected for protein/mRNA analysis. Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, matrix metalloproteinase-2 (MMP-2) and MMP-9 proteins were measured using enzyme-linked immunosorbent assay and mRNAs by RT-PCR. Phosphorylation of p38 MAPK was evaluated by western blotting. RESULTS SB203580 decreased the weight and size (P < 0.05 versus EM) of endometriotic lesions in BALB/c mice. IL-1β, TNF-α, MMP-2 and MMP-9 mRNA levels were decreased in peritoneal cells of the SB203580 versus EM group (P < 0.01, P < 0.05, P < 0.05 and P < 0.05, respectively). Concentrations of IL-1β, TNF-α, MMP-2 and MMP-9 proteins in PF were reduced in the SB203580 versus EM group (P < 0.05, P < 0.01, P < 0.05 and P < 0.05, respectively). Compared with the sham-operated group, phosphorylation of p38 MAPK in the EM group was increased, and this was down-regulated by SB203580 (P < 0.01). CONCLUSIONS SB203580 may suppress the development of EM by inhibiting expression of proinflammatory cytokines and proteolytic factors. p38 MAPK might play a key role in progression of EM.

Hum Reprod. 2010 Dec;25(12):3043-9. Epub 2010 Oct 11.

Expression and possible role of non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) in the human endometrium and endometriosis.

Seo SK, Nam A, Jeon YE, Cho S, Choi YS, Lee BS.

Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University, College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul 120-752, South Korea.

BACKGROUND Non-steroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1) is involved in cellular processes such as inflammation, apoptosis and tumorigenesis. However, little is known about the expression and function of NAG-1 in the endometrium. This study aimed to evaluate the expression of NAG-1 in the endometrium and in the absence or presence of endometriosis and to investigate the effect of celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, on NAG-1 mRNA levels and apoptosis in human endometrial stromal cells (HESCs). METHODS Eutopic endometrial samples were obtained during surgery from 40 patients with, and 40 patients without, endometriosis. Real-time PCR was used to quantify NAG-1 mRNA levels and immunohistochemistry was used to localize NAG-1 protein in the endometrium. To investigate the effects of celecoxib, HESCs were isolated and cultured with different concentrations of celecoxib or with 100 µM celecoxib at different times. Apoptosis was assessed by flow cytometry. RESULTS NAG-1 mRNA levels and immunoreactivity showed cyclical changes through the menstrual cycle, increasing during the late secretory and menstrual phases. NAG-1 mRNA and protein levels were significantly lower in patients with endometriosis, compared with the control group. Celecoxib induced NAG-1 mRNA levels and apoptosis in cultured HESCs, with the effects dependent on drug concentrations and duration of treatment. Celecoxib treatment had no effect on prostaglandin E(2) levels in the culture supernatants. CONCLUSIONS NAG-1 may be important in maintaining homeostasis in the normal endometrium and alterations in NAG-1 expression may be associated with the establishment of endometriosis. NAG-1 might be a therapeutic target for endometriosis.

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