J Obstet Gynaecol Res. 2010 Feb;36(1):1-10.

Mysteries of endometriosis pain: Chien-Tien Hsu Memorial Lecture 2009.

Fraser IS.

Department of Obstetrics and Gynaecology, University of Sydney, Sydney, New South Wales, Australia.

The more that one looks at the condition endometriosis, the more one realises that it is a unique and complex condition exhibiting a bizarre range of deviations from normal endometrial and myometrial physiology, and presenting with a challenging range of pain-related symptoms. The changing nature of the pain is not well defined, and the molecular mechanisms leading to pain generation are far from clear. Recent research has begun to reveal some of these links between expression of unusual molecules in the eutopic endometrium and ectopic lesions, microanatomical changes in the pelvic nervous sytem, neuronal dysfunction and the later development of neuropathic pain. A better understanding of these mechanisms will undoubtedly lead to improved use of current medical and surgical treatments, and to the development of novel treatments in the future.

Hum Reprod. 2010 Feb 22. [Epub ahead of print]

Inflammatory cytokines differentially up-regulate human endometrial haptoglobin production in women with endometriosis{dagger}

Sharpe-Timms KL, Nabli H, Zimmer RL, Birt JA, Davis JW.

Department of Obstetrics, Gynecology and Women’s Health, The University of Missouri – Columbia, 1 Hospital Drive, N 625 HSC, Columbia, MO 65212, USA.

BACKGROUND Evidence suggests that eutopic endometrium from women with endometriosis (US-E) has intrinsic functional anomalies compared with women without endometriosis (US-C). We hypothesized that differences in endometrial haptoglobin (eHp) mRNA and protein levels exist between eutopic endometrium from US-E and US-C and that inflammatory mediators may be involved. METHODS Endometrial stromal cells and tissue explants from US-E (n = 18) and US-C (n = 18) were cultured (24 h/48 h for cells/explants) with interleukin (IL)-1alpha, -1beta, -6, -8 or tumor necrosis factor-alpha (TNF-alpha) at 0-100 ng/ml. eHp protein in media and mRNA levels were quantified by enzyme-linked immunosorbent assay and quantitative PCR. RESULTS In eutopic endometrial stromal cells from US-E, IL-1beta, IL-6 and TNF-alpha (10 ng/ml) increased eHp mRNA levels (P = 0.002, P < 0.001 and P < 0.001, respectively) and eHp protein (P = 0.023, 0.031 and 0.006, respectively) versus control. In endometrial tissues from US-E, IL-1beta, IL-6 and TNF-alpha increased eHp mRNA (P < 0.001, P = 0.017 and P < 0.001, respectively) and eHp protein (P < 0.001, P = 0.007 and 0.039, respectively) versus control. IL-1alpha and IL-8 had small or no effects on isolated endometrial cells or tissues. In US-C, IL-1beta, IL-8 and TNF-alpha each reduced eHp mRNA in endometrial stromal cells (all P < 0.001) versus control; IL-1alpha and IL-6 had no effect. eHp mRNA increased in endometrial tissues from US-C in response to IL-1beta (P = 0.008), IL-6 (P = 0.015) and TNF-alpha (P = 0.031) versus control; IL-1alpha or IL-8 had no effect. CONCLUSIONS Endometrium from US-E differentially responds to specific inflammatory cytokines by production of eHp. We propose that up-regulation of endometrial eHp by inflammatory mediators disrupts normal endometrial function and may facilitate the pathogenesis of endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2010 Feb 20. [Epub ahead of print]

Effect of palmitoylethanolamide-polydatin combination on chronic pelvic pain associated with endometriosis: Preliminary observations.

Indraccolo U, Barbieri F.

Department of Surgical Sciences, Institute of Obstetrics and Gynaecology, University of Foggia. Via Pinto, 71100 Foggia, Italy; Obstetrics and Gynaecology Unit, ULSS 17 – Veneto, Italy.

OBJECTIVE: Endometriosis is a chronic oestrogen-dependent gynaecological disorder, the most common symptom of which is pain. Inflammation can be considered one of the major causes of pain in endometriosis. In particular, degranulating mast cells have been found in significantly greater quantities in endometriotic lesions than in unaffected tissues. The increase in activated and degranulating mast cells is closely associated with nerve structures in painful endometriotic lesions. These observations indicate that inflammation due to mast cells may contribute to the development of pain and hyperalgesia in endometriosis. Controlling mast-cell activation may therefore relieve the pain associated with endometriotic lesions. STUDY DESIGN: Four patients presenting an endometriosis-related pain intensity >/=5 (visual analogue scale for pain, or VAS) were enrolled and monitored during 3 months of the following treatment: oral palmitoylethanolamide 400mg and polydatin 40mg, twice daily for 90 days. Deep dyspareunia, dyschezia, dysuria, dysmenorrhoea and analgesic drug use during the 3-month follow-up period were also monitored, with the aim of demonstrating a reliable reduction in chronic pelvic pain. RESULTS: The preliminary results indicate that all patients enrolled experienced pain relief as early as 1 month after starting treatment. Furthermore, a reduction in the analgesic drugs usually employed for pain control was observed in all subjects treated. Additionally, some improvements in endometriotic lesions seemed to be demonstrated by imaging. CONCLUSIONS: The palmitoylethanolamide-polydatin combination seems to be very useful in controlling chronic pelvic pain associated with endometriosis. As a result of these findings we have initiated a multi-centre pilot study to verify the effectiveness of this treatment in controlling the chronic pelvic pain associated with endometriosis. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

J Mol Med. 2010 Feb 20. [Epub ahead of print]

Stress, inflammation and endometriosis: are patients stuck between a rock and a hard place?

Toth B.

Department of Gynecological Endocrinology and Reproductive Medicine, Ruprecht Karl-University Heidelberg, Vossstr. 9, 69115, Heidelberg, Germany, bettina.toth@med.uni-heidelberg.de.

Int J Gynecol Pathol. 2010 Mar;29(2):185-8.

Polypoid endometriosis of the uterine cervix with arias-stella reaction in a patient taking phytoestrogens.

Félix A, Nogales FF, Arias-Stella J.

Serviço de Anatomia Patológica (A.F.), Instituto Português de Oncologia de Lisboa Francisco Gentil, Cedoc, Faculdade de Ciências Médicas, Universidade Nova de Lisboa Portugal Departamento de Anatomía Patológica (F.F.N.), Universidad de Granada, Spain Facultad de Medicina (J.A-S.), Universidad Peruana Cayetano Heredia, Instituto de Patología y Biología Molecular Arias Stella, Lima, Peru.

We report for the first time a case of 2.5 cm polypoid cervical endometriosis with a superficial growth pattern in a 48-year-old patient with past tubal ligation. The lesion showed metaplastic changes (clear cell, eosinophilic, micropapillary) and a prominent Arias Stella reaction in the absence of concomitant pregnancy but presumably related to phytoestrogenic treatment. The eutopic endometrium, however, had a usual proliferative appearance, implying that it showed a different response from the endometriotic tissues, suggesting the possibility of a metaplastic origin for the endocervical polypoid endometriosis. The unusual histology of the lesion led to an erroneous diagnosis of papillary serous carcinoma in the biopsy. This was subsequently excluded on finding endometrial-type stroma surrounding glands, and was confirmed immunohistochemically by a low Ki-67 index and negativity for p53.

Hum Reprod. 2010 Feb 19. [Epub ahead of print]

The roles of thioredoxin and thioredoxin-binding protein-2 in endometriosis.

Seo SK, Yang HI, Lee KE, Kim HY, Cho S, Choi YS, Lee BS.

Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University, College of Medicine, 146-92 Dogok-dong, Gangnam-gu, Seoul 135-720, Korea.

BACKGROUND Oxidative stress is considered to be involved in the establishment and development of endometriosis. Thioredoxin (TRX) is an endogenous redox regulator that protects cells against oxidative stress, and TRX-binding protein-2 (TBP-2) is a negative regulator of TRX in the biological function and expression. The aim of this study was to investigate the roles of TRX and TBP-2 in the pathophysiology of endometriosis. METHODS A total of 35 patients with histologically confirmed endometriosis and 31 patients without endometriosis participated in this study. Real-time polymerase chain reaction was used to quantify TRX and TBP-2 mRNA levels, and immunohistochemistry (IHC) was used to assess TRX and TBP-2 protein localization in the endometrium. Serum and peritoneal fluid levels of TRX and TBP-2 were measured using a specific commercial ELISA. RESULTS There were no significant differences in TRX mRNA levels in the endometrium of patients with endometriosis and the control groups. However, TBP-2 mRNA levels in the endometrium were lower, and the TRX to TBP-2 ratio was higher in patients with endometriosis than in the control group. In particular, the TRX to TBP-2 ratio was significantly higher during late secretory and menstrual phase in patients with endometriosis compared with the control group. IHC studies also showed the decreased TBP-2 immunoreactivity in patients with endometriosis compared with the control group. There was no correlation between TRX and TBP-2 mRNA levels in patients with endometriosis, whereas TRX mRNA levels were positively correlated with TBP-2 mRNA levels in the control group. There were no significant differences between the two groups in TRX and TBP-2 levels in serum or peritoneal fluid. CONCLUSIONS Aberrant expression of TRX and TBP-2 in the endometrium may be associated with the establishment of endometriosis.

Hum Reprod. 2010 Feb 19. [Epub ahead of print]

A prospective study of body size during childhood and early adulthood and the incidence of endometriosis.

Vitonis AF, Baer HJ, Hankinson SE, Laufer MR, Missmer SA.

Obstetrics and Gynecology Center, Brigham and Women’s Hospital, 221 Longwood Avenue, Boston, MA 02115, USA.

BACKGROUND An inverse association between adult body mass index (BMI) and risk of endometriosis has frequently been reported. However, the association between body size during childhood and early adulthood and endometriosis is not as well documented. METHODS Using data collected from the Nurses’ Health Study II, a prospective cohort study of premenopausal US nurses, that began in 1989, we have attempted to clarify this relationship. Data are updated every 2 years with follow-up for these analyses through 2001. In 1989 women recalled their body size at ages 5, 10 and 20 years using a validated 9-level figure drawing. RESULTS During 831 910 person-years of follow-up, 1817 cases of self-reported laparoscopically-confirmed endometriosis were observed among women with no past infertility. After adjusting for age, birthweight, age at menarche, parity, oral contraceptive use and adult BMI, we observed a significant reduction in the incidence of endometriosis with increasing body size for all time periods. The relative risks (RRs) comparing the smallest and largest figure sizes to the middle category during childhood (ages 5-10) were 1.18 (95% confidence interval 1.02-1.36) and 0.82 (0.66-1.02), P-trend = 0.0002. At age 20, the RRs for the same comparisons were 1.32 (1.06-1.65) and 0.87 (0.74-1.03), P-trend = 0.04. Additional adjustment by menstrual cycle length and regularity yielded similar associations. The associations were stronger among nulliparous women than among parous women, although not all differences were statistically significant. CONCLUSION In this large cohort of premenopausal women, there was evidence of a persistent inverse association between childhood and early adulthood body size and incidence of laparoscopically confirmed endometriosis, independent of adult BMI and menstrual cycle characteristics.

Eur J Radiol. 2010 Feb 18. [Epub ahead of print]

Learning curve in the detection of ovarian and deep endometriosis by using Magnetic Resonance Comparison with surgical results.

Saba L, Guerriero S, Sulis R, Pilloni M, Ajossa S, Melis G, Mallarini G.

Department of Science of the Images, Azienda Ospedaliero Universitaria di Cagliari, s.s. 554 Monserrato (Cagliari) 09045, Italy.

PURPOSE: Determining if Magnetic Resonance Imaging (MRI) accuracy in diagnosing endometriosis is related to radiologist’s expertise. METHODS AND MATERIALS: Written informed consent was obtained from all patients. This study is compliant to STARD method. Thirty patients (mean age 34; range 21-45 years) who had undergone MRI study for suspected endometriosis underwent surgery were retrospectively evaluated. MRI at 1.5T was performed with SE and TSE sequences, T1 and T2-weighted with and without fat suppression. Four localizations were analyzed: ovary, uterosacral ligaments (USL), vaginal fornix and RectumSigmaDouglas (R.S.D.). One radiologist evaluated each dataset; sensitivity, specificity, PPV and NPV, accuracy, LR+ and LR- were calculated according to the surgical results (first analysis). Dataset were then re-analyzed 12 months (second analysis) and 24 months (third analysis) later. McNemar test was applied to determine differences between the three analysis. RESULTS: Sensitivity, specificity and accuracy for the ovary at the first analysis were 88.9%, 87% and 88%, at the second 92.6%, 87% and 90% whereas at the third 92.6%, 91.3% and 92%. Sensitivity, specificity and accuracy for the USLs at the first analysis were 62.5%, 76.9% and 70%, at the second 72%, 80.8% and 76% whereas at the third 80%, 84.6% and 82%. Sensitivity, specificity and accuracy for the vaginal fornix at the first analysis were 63.2%, 64.5% and 64%, at the second 73.7%, 77.4% and 76% whereas at the third 73.7%, 83.9% and 80%. Sensitivity, specificity and accuracy for the R.S.D. at the first analysis were 39.1%, 81.5% and 62%, at the second 62.5%, 85.2% and 76% whereas at the third 73.9%, 88.9% and 82%. McNemar test indicated a significant statistical difference in sensitivity in detecting nodules of endometriosis in R.S.D. between first and third analysis (p=0.0215). The mean review time decreased (p=0.0001). CONCLUSIONS: Accuracy of MRI in diagnosing endometriosis increased with radiologist’s expertise and the improvement was statistically significant in determining RSD involvement. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Fertil Steril. 2010 Feb 18. [Epub ahead of print]

Differential expression of genes from the homeobox A cluster in deep endometriotic nodules and peritoneal lesions.

Van Langendonckt A, Luyckx M, Gonzalez MD, Defrère S, Donnez J, Squifflet J.

Department of Gynecology, Université Catholique de Louvain, 1200 Brussels, Belgium.

OBJECTIVE: To compare expression of homeobox A (HOXA) genes involved in the differentiation of the female reproductive tract in deep endometriotic nodules and peritoneal lesions. DESIGN: Prospective experimental study. SETTING: Academic gynecology research unit. PATIENT(S): Thirty patients undergoing laparoscopy. INTERVENTION(S): During laparoscopy, deep endometriotic nodules (n = 30) and peritoneal lesions (n = 11) were recovered. Eutopic endometrium and vaginal tissue (n = 30) were collected for control purposes. MAIN OUTCOME MEASURE(S): Quantification of HOXA-9, HOXA-10, HOXA-11, and HOXA-13 in deep nodules, peritoneal lesions, and control samples by real-time reverse-transcription polymerase chain reaction, and localization of HOXA-10 and HOXA-13 proteins by immunohistochemistry. RESULT(S): The HOXA-13 transcripts were detected in 29 out of 30 nodules, and their expression was significantly higher than in vaginal tissue, but they were barely detectable in endometrium and peritoneal lesions. Expression of HOXA-10 and HOXA-11 transcripts in deep nodules was similar to eutopic endometrium, and HOXA-10 expression was significantly lower in peritoneal endometriotic lesions. The HOXA-10 immunostaining was mainly localized in the stroma of deep endometriotic nodules, HOXA-13 in glandular structures and stroma, and neither of these proteins were detected in fibromuscular areas. CONCLUSION(S): Marked expression of HOXA-10 and HOXA-13 in the endometrium-like tissue of nodules but low expression in peritoneal endometriotic lesions supports the theory of differential origin of these two types of endometriosis. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Abdom Imaging. 2010 Feb 19. [Epub ahead of print]

Anterior pelvic endometriosis: MRI features.

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

Service d’Imagerie diagnostique et interventionnelle, Centre Hospitalier Régional et Universitaire de Nice, Hôpital Archet 2, 151 route de Saint Antoine de Ginestière, B.P 3079, 06202, Nice Cedex 3, France, novellas.s@chu-nice.fr.

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.

Obstet Gynecol. 2009 Nov;114(5):1041-8.

Nationwide use of laparoscopic hysterectomy compared with abdominal and vaginal approaches.

Jacoby VL, Autry A, Jacobson G, Domush R, Nakagawa S, Jacoby A.

From the 1University of California, San Francisco, Department of Obstetrics, Gynecology, and Reproductive Sciences, and the 2Department of Obstetrics and Gynecology, Kaiser Permanente Northern California, San Francisco, California.

OBJECTIVE:: To examine factors associated with undergoing laparoscopic hysterectomy compared with abdominal hysterectomy or vaginal hysterectomy. METHODS:: This is a cross-sectional analysis of the 2005 Nationwide Inpatient Sample. All women aged 18 years or older who underwent hysterectomy for a benign condition were included. Multivariable analyses were used to examine demographic, clinical, and health-system factors associated with each hysterectomy route. RESULTS:: Among 518,828 hysterectomies, 14% were laparoscopic, 64% abdominal, and 22% vaginal. Women older than 35 years had lower rates of laparoscopic than abdominal (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.77-0.94 for age 45-49 years) or vaginal hysterectomy (OR 0.61, 95% CI 0.540.69 for age 45-49 years). The odds of laparoscopic compared with abdominal hysterectomy were higher in the West than in the Northeast (OR 1.77, 95% CI 1.2-2.62). African-American, Latina, and Asian women had 40-50% lower odds of laparoscopic compared with abdominal hysterectomy (P<.001). Women with low income, Medicare, Medicaid, or no health insurance were less likely to undergo laparoscopic than either vaginal or abdominal hysterectomy (P<.001). Women with leiomyomas (P<.001) and pelvic infections (P<.001) were less likely to undergo laparoscopic than abdominal hysterectomy. Women with leiomyomas (P<.001), endometriosis (P<.001), or pelvic infections (P<.001) were more likely to have laparoscopic than vaginal hysterectomy. Laparoscopic hysterectomy had the highest mean hospital charges ($18,821, P<.001) and shortest length of stay (1.65 days, P<.001). CONCLUSION:: In addition to age and clinical diagnosis, nonclinical factors such as race/ethnicity, insurance status, income, and region appear to affect use of laparoscopic hysterectomy compared with abdominal hysterectomy and vaginal hysterectomy. LEVEL OF EVIDENCE:: III.

Gynecol Obstet Invest. 2010 Feb 16;70(1):34-39. [Epub ahead of print]

Intercellular Adhesion Molecule-1 and Interleukin-6 Gene Polymorphisms in Patients with Advanced-Stage Endometriosis.

Chae SJ, Lee GH, Choi YM, Hong MA, Kim JM, Lee KS, Ku SY, Moon SY.

Maria Fertility Hospital, Gachon University of Medicine and Science, Incheon, Korea.

Background/Aims: The aim of this study was to investigate the possibility that the K469E and G241R polymorphisms in the intercellular adhesion molecule-1 (ICAM-1) gene and the C-634G polymorphism in the interleukin (IL)-6 gene are associated with endometriosis in the Korean population. Methods: The ICAM-1 gene K469E and G241R polymorphisms and the IL-6 gene C-634G polymorphism were evaluated in 390 patients with endometriosis and 351 controls by polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The ICAM-1 gene G241R polymorphism was not observed in all subjects. No differences were observed in the ICAM-1 K469E and IL-6 C-634G genotype distributions and allele frequencies between patients with endometriosis and controls. In subgroup analyses according to the stage of endometriosis or bilaterality of ovarian endometriomas, no significant differences were observed in the ICAM-1 gene K469E or the IL-6 gene C-634G polymorphism frequencies between the subgroups and the controls. The combined analysis of the ICAM-1 gene K469E polymorphism and the IL-6 gene C-634G polymorphism did not show any additional significant findings. Conclusions: The K469E and G241R polymorphisms in the ICAM-1 gene and the C-634G polymorphism in the IL-6 gene may not be genetic factors related to susceptibility to advanced-stage endometriosis in the Korean population. Copyright © 2010 S. Karger AG, Basel.

Endocrinology. 2010 Feb 16. [Epub ahead of print]

Peroxisome Proliferator-Activated Receptor-{gamma} Receptor Ligand Partially Prevents the Development of Endometrial Explants in Baboons: A Prospective, Randomized, Placebo-Controlled Study.

Lebovic DI, Mwenda JM, Chai DC, Santi A, Xu X, D’Hooghe T.

Reproductive Endocrinology and Infertility Division (D.I.L.), Department of Obstetrics and Gynecology, University of Wisconsin, Madison, Wisconsin 53792; Institute of Primate Research (J.M.M., D.C.C., T.D.), Karen 00502, Nairobi, Kenya; Endometriosis Center (A.S.), Department of Obstetrics and Gynecology, University of Berne, Berne, Switzerland; Health Services Research Group (X.X.), Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan 48109; and Leuven University Fertility Center (T.D.), Department of Obstetrics and Gynecology, University Hospital Gasthuisberg, 3000 Leuven, Belgium.

A prospective, randomized, placebo-controlled study was conducted in a baboon model to determine if a thiazolidinedione agonist of peroxisome proliferator-activated receptor-gamma, pioglitazone, can impede the development of endometriosis. Endometriosis was induced using laparoscopic, intrapelvic injection of eutopic menstrual endometrium, previously incubated with placebo or pioglitazone for 30 min, in 12 female baboons with a normal pelvis that had undergone at least one menstrual cycle since the time of captivity. At this point, the 12 baboons were randomized into two groups and treated from the day of induction. They received either PBS tablets (n = 6, placebo control, placebo tablets once a day by mouth) or pioglitazone (n = 6, test drug, 7.5 mg by mouth each day). A second and final laparoscopy was performed in the baboons to record the extent of endometriotic lesions between 24 and 42 d after induction (no difference in length of treatment between the two groups, P = 0.38). A videolaparoscopy was performed to document the number and surface area of endometriotic lesions. The surface area and volume of endometriotic lesions were significantly lower in pioglitazone treated baboons than the placebo group (surface area, 48.6 vs. 159.0 mm(2), respectively, P = 0.049; vol, 23.7 vs. 131.8 mm(3), respectively, P = 0.041). The surface area (3.5 vs. 17.8 mm(2), P = 0.017, pioglizatone vs. placebo) and overall number (1.5 vs. 9.5, P = 0.007, pioglizatone vs. placebo) of red lesions were lower in the pioglitazone group. A peroxisome proliferator-activated receptor-gamma ligand, pioglitazone, effectively reduced the initiation of endometriotic disease in the baboon endometriosis model. Using this animal model, we have shown that thiazolidinedione is a promising drug for preventive treatment of endometriosis.

Virchows Arch. 2010 Feb 13. [Epub ahead of print]

Immunohistochemical detection of steroid receptor cofactors in ovarian endometriosis: involvement of down-regulated SRC-1 expression in the limited growth activity of the endometriotic epithelium.

Suzuki A, Horiuchi A, Oka K, Miyamoto T, Kashima H, Shiozawa T.

Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.

To study the steroid hormone-induced growth mechanisms of endometriosis, the immunohistochemical expression of steroid hormone receptor cofactors was investigated in 37 cases of endometriotic epithelia and was compared with that of eutopic endometria of identical patients. The expression of steroid receptor coactivators (p300/CBP and SRC-1) and corepressors (NCoR and SMRT) was examined in relation to the estrogen receptor (ER), the progesterone receptor (PR), and Ki-67. Results of immunostaining were indicated as a “positivity index” (PI, full score; 100). The expression of ER and PR in endometriotic epithelia largely resembled that in eutopic endometria, however, the expression of Ki-67 in the proliferative phase (PI 13.8 +/- 2.4, mean +/- SD) was significantly lower than that in eutopic endometria (32.6 +/- 10.6). The expression of SRC-1 in eutopic endometria was increased in the proliferative phase (56.5 +/- 16.8) and decreased in the secretory phase (14.8 +/- 6.9). In endometriosis, however, the PI for SRC-1 did not show apparent cyclic changes during the menstrual cycle. Moreover, the expression of SRC-1 in endometriotic epithelia in the proliferative phase was significantly lower than that in eutopic endometria. These findings suggested the reduced proliferative activity in endometriotic epithelia to be related to the reduced expression of SRC-1.

Am J Surg Pathol. 2010 Feb 11. [Epub ahead of print]

The Origin and Pathogenesis of Epithelial Ovarian Cancer: A Proposed Unifying Theory.

Kurman RJ, Shih IM.

Departments of Pathology, Gynecology and Obstetrics and Oncology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.

Ovarian cancer is the most lethal gynecologic malignancy. Efforts at early detection and new therapeutic approaches to reduce mortality have been largely unsuccessful, because the origin and pathogenesis of epithelial ovarian cancer are poorly understood. Despite numerous studies that have carefully scrutinized the ovaries for precursor lesions, none have been found. This has led to the proposal that ovarian cancer develops de novo. Studies have shown that epithelial ovarian cancer is not a single disease but is composed of a diverse group of tumors that can be classified based on distinctive morphologic and molecular genetic features. One group of tumors, designated type I, is composed of low-grade serous, low-grade endometrioid, clear cell, mucinous and transitional (Brenner) carcinomas. These tumors generally behave in an indolent fashion, are confined to the ovary at presentation and, as a group, are relatively genetically stable. They lack mutations of TP53, but each histologic type exhibits a distinctive molecular genetic profile. Moreover, the carcinomas exhibit a shared lineage with the corresponding benign cystic neoplasm, often through an intermediate (borderline tumor) step, supporting the morphologic continuum of tumor progression. In contrast, another group of tumors, designated type II, is highly aggressive, evolves rapidly and almost always presents in advanced stage. Type II tumors include conventional high-grade serous carcinoma, undifferentiated carcinoma, and malignant mixed mesodermal tumors (carcinosarcoma). They displayTP53 mutations in over 80% of cases and rarely harbor the mutations that are found in the type I tumors. Recent studies have also provided cogent evidence that what have been traditionally thought to be primary ovarian tumors actually originate in other pelvic organs and involve the ovary secondarily. Thus, it has been proposed that serous tumors arise from the implantation of epithelium (benign or malignant) from the fallopian tube. Endometrioid and clear cell tumors have been associated with endometriosis that is regarded as the precursor of these tumors. As it is generally accepted that endometriosis develops from endometrial tissue by retrograde menstruation, it is reasonable to assume that the endometrium is the source of these ovarian neoplasms. Finally, preliminary data suggest that mucinous and transitional (Brenner) tumors arise from transitional-type epithelial nests at the tubal-mesothelial junction by a process of metaplasia. Appreciation of these new concepts will allow for a more rationale approach to screening, treatment, and prevention that potentially can have a significant impact on reducing the mortality of this devastating disease.

Fertil Steril. 2010 Feb 11. [Epub ahead of print]

Evaluation of erythrocyte band 3 phosphotyrosine level, glutathione content, CA-125, and human epididymal secretory protein E4 as combined parameters in endometriosis.

Bordin L, Fiore C, Donà G, Andrisani A, Ambrosini G, Diego F, Plebani M, Clari G, Armanini D.

Department of Biological Chemistry, University of Padova, Padova, Italy.

OBJECTIVE: To investigate the biochemical parameters of the erythrocyte response to diamide-induced oxidative stress, alone or as adjuncts to serum values of CA-125 and human epididymal secretory protein E4 (HE4), in the diagnosis and study of endometriosis. SETTING: University of Padova. DESIGN: Prospective study. PATIENT(S): Forty-five patients of reproductive age undergoing laparoscopy. INTERVENTION(S): All women were studied for endometriotic foci during laparoscopic surgery. Forty-one had laparoscopically and histologically confirmed endometriosis, and four did not. Twenty women with confirmed endometriosis were reassessed 1-4 months later. MAIN OUTCOME MEASURE(S): CA-125 and HE4 and two new parameters evaluated in erythrocytes after diamide-induced stress, that is, band 3 tyrosine phosphorylation (Tyr-P) level and decrease in total glutathione content (DeltaGSH), were assessed in all patients. RESULT(S): In association with serum CA-125 levels but not with HE4, diamide-related erythrocyte band 3 Tyr-P and DeltaGSH were significantly higher in patients with endometriosis and were able to discriminate with high sensitivity and specificity between patients before and after surgery. CONCLUSION(S): Endometriosis is associated with an increase in systemic oxidative stress, affecting the antioxidative defenses of circulating erythrocytes. All related implications, including evaluation of other oxidative stress-related changes, warrant further study. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Hum Reprod. 2010 Feb 10. [Epub ahead of print]

The role of Foxp3+ regulatory T-cells in endometriosis: a potential controlling mechanism for a complex, chronic immunological condition.

Berbic M, Hey-Cunningham AJ, Ng C, Tokushige N, Ganewatta S, Markham R, Russell P, Fraser IS.

Department of Obstetrics and Gynaecology, Queen Elizabeth II Research Institute for Mothers and Infants, the University of Sydney, New South Wales, Australia.

BACKGROUND Endometriosis is an inflammatory condition, associated with highly dysregulated immune response at both uterine and peritoneal levels. Surprisingly, Foxp3+ regulatory T-cells, which control and suppress a range of immune responses, have not previously been investigated in endometriosis. METHODS AND RESULTS Immunohistochemical analysis of Foxp3+ cells in 127 eutopic endometrial samples and 59 ectopic peritoneal lesions revealed that these immune cell populations are highly disturbed in women suffering from endometriosis. We showed that Foxp3+ cells remained highly up-regulated during the secretory phase of the menstrual cycle, while at this time their expression is significantly down-regulated in women without endometriosis (P < 0.001). Foxp3+ cells were detected in the stroma of 18 of the 59 peritoneal endometriotic lesions, but not in the surrounding or control peritoneal tissue. CONCLUSIONS We propose that in eutopic endometrium in women with endometriosis Foxp3+ cells decrease the ability of newly recruited immune cell populations to effectively recognize and target endometrial antigens shed during menstruation, allowing their survival and ability to implant in ectopic sites. At these ectopic sites, variable expression of Foxp3+ cells within some peritoneal endometriotic lesions is likely to be linked to the characteristics and stage of individual lesion development and be playing key roles in pathogenesis and progression of this unique condition.

Fertil Steril. 2010 Feb 9. [Epub ahead of print]

Magnetic resonance neurography for the diagnosis of extrapelvic sciatic endometriosis.

Pham M, Sommer C, Wessig C, Monoranu CM, Pérez J, Stoll G, Bendszus M.

Department of Neuroradiology, University of Heidelberg, Heidelberg; Department of Neuroradiology,University of Würzburg, Würzburg, Germany.

OBJECTIVE: To illustrate magnetic resonance neurography findings of severe sciatic injury and muscle denervation related to deep gluteal endometriosis at the sciatic notch. DESIGN: Case report. SETTING: Academic teaching hospital. PATIENT(S): A 39-year-old woman with a 4-year history of sciatica related to the menstrual cycle. INTERVENTION(S): Surgical exploration of the sciatic notch for diagnostic confirmation, external neurolysis of the sciatic nerve, and eventual pharmacologic treatment. MAIN OUTCOME MEASURE(S): Magnetic resonance neurography imaging revealed severe neuropathic injury and muscle denervation related to a deep infiltrative endometriotic focus at the sciatic notch, which was confirmed histologically on surgical exploration. Detailed electrodiagnostic and clinical neurologic examinations at initial presentation and during follow-up were obtained for further assessment of nerve degeneration, muscle denervation, and clinical recovery. RESULT(S): Initial gynecologic and eventual laparoscopic evaluation on persisting complaints were without pathological findings. When a progressive weakness of the leg was noted, magnetic resonance neurography revealed a severe axonal damage to the sciatic nerve and denervation of distal target muscles related to a diffuse infiltrative lesion at the sciatic notch. On surgical exploration, extragenital endometriosis was confirmed histologically. Considerable improvement in pain and strength occurred after pharmacologic therapy with a GnRH analogue. CONCLUSION(S): This is the first report to describe imaging findings of magnetic resonance neurography in severe neuropathic injury of the sciatic nerve and subsequent muscle denervation related to a deep infiltrative gluteal endometriotic focus. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

J Obstet Gynaecol Res. 2009 Oct;35(5):994-6.

Endometriosis in a patient with Rokitansky-Kuster-Hauser syndrome.

Cho MK, Kim CH, Oh ST.

Department of Obstetrics and Gynecology, Chonnam National University Medical School, Gwangju, Korea.

Endometriosis in Rokitansky-Kuster-Hauser syndrome has been reported only once previously. We present here a case of endometrioma in a patient with Rokitansky-Kuster-Hauser syndrome. A 26-year-old patient with Rokitansky-Kuster-Hauser syndrome presented with abrupt pain in the left iliac quadrant. A mass was confirmed by sonography. Laparoscopic inspection revealed no uterus. The mass was removed laparoscopically. Endometriosis was confirmed histologically. If endometrioma in a patient with Rokitansky-Kuster-Hauser syndrome is associated with a small rudimentary unicornis uterus with a small endometrial cavity, endometriosis can be assumed to have developed by retrograde menstruation theory. Because the patient did not have a functioning endometrium, her endometrioma is assumed to have arisen from coelomic metaplasia.

J Obstet Gynaecol Res. 2009 Oct;35(5):935-9.

Massive peritoneal fluid and markedly elevated serum CA125 and CA19-9 levels associated with an ovarian endometrioma.

Park BJ, Kim TE, Kim YW.

Department of Obstetrics and Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Endometriosis associated with ascites is an uncommon condition, but nevertheless important because it mimics the presentation of ovarian malignancy. We present the case of a 34-year-old woman who was admitted with the acute onset of abdominal pain and distension. A pelvic sonogram showed a large amount of peritoneal fluid with echogenic material and a 10-cm complex cystic structure, which appeared to be an enlarged left ovary. The concentrations of CA125 and CA19-9 were 548.1 and 7604 IU/mL, respectively. On the second day of admission, an exploratory laparoscopy was performed, which revealed a ruptured left ovarian cyst consistent with an endometrioma. A laparoscopic left adnexectomy was therefore performed. The histological examination of the specimen confirmed the diagnosis of an endometrioma. After a 12-month follow-up period, the patient showed no recurrence of the endometrioma or peritoneal fluid accumulation. In most instances, the presence of massive ascites is associated with malignancies, tuberculosis, or a perforated viscus. The information provided in the present report is important to both gynecologists and oncologists because it shows that an ovarian cyst with ascites and highly elevated CA125 and CA19-9 levels might be benign.

J BUON. 2009 Oct-Dec;14(4):699-701.

Association of endometriosis with family history of non-Hodgkin’s lymphoma: presentation of 10 cases.

Matalliotakis I, Cakmak H, Fragouli Y, Zervoudis S, Neonaki M, Arici A.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA. matakgr@yahoo.com

PURPOSE: Women with endometriosis have been reported to be at increased risk of developing non-Hodgkin’s lymphoma (NHL). The purpose of this article was to investigate the familial risk of NHL in women with endometriosis. We report on 10 cases with endometriosis and positive family history of NHL. METHODS: The medical records of 405 women with endometriosis and 200 without endometriosis were retrospectively analysed. All of the cases were diagnosed by laparoscopy. Ten cases of endometriosis having first-degree relatives with NHL are reported. RESULTS: We found no case with endometriosis and NHL. In contrast, we found 10/405 (2.5%) women with endometriosis and first-degree relatives with NHL. Their mean age was 38.3 years (range 29-46). The main complaint was infertility. The mean age at onset of endometriosis was 32 years (range 22-43). The stages of endometriosis were: stage II (n=4), stage III (n=2) and stage IV (n=4). All of these patients had first-degree relatives with a history of NHL. Five had mothers with NHL, 5 had fathers and one had a sister. CONCLUSION: These cases could suggest a link between a family history of NHL and subsequent development of endometriosis in the first-generation women. Moreover, there was no evidence of association between endometriosis and NHL.

Biol Reprod. 2010 Feb 10. [Epub ahead of print]

Hepatocyte Growth Factor System in the Mouse Uterus: Variation Across the Estrous Cycle and Regulation by 17-Beta-Estradiol and Progesterone.

Zhang X.

Hepatocyte growth factor (HGF) and its receptor MET have been implicated in uterine development, pregnancy, and endometrial disorders such as endometriosis and carcinoma. In vitro studies have shown that HGF acts as a mitogen, motogen and morphogen on endometrial epithelial cells. However, the expression and regulation of HGF and MET in the uteri of different species remain obscure. This study aims to investigate the changes of HGF, MET and HGF activator (HGFA) expression in the uterine endometrium during the estrous cycle in mice and to explore estrogen and progesterone regulation of their expression. MKI67 immunostaining was conducted to examine the association between HGF/MET expression and endometrial cell proliferation. It was found that endometrial epithelial and stromal cells both expressed HGF, HGFA and MET, but the cell type-specific patterns changed during the cycle. Estrogen and progesterone differentially regulated HGF, MET and HGFA expression. P4 up-regulated their expression in the stroma and down-regulated them in the luminal epithelium, while 17-beta-estradiol down-regulated them in the glandular epithelium. The pattern of HGF/MET overall correlated with MKI67. In conclusion, HGF, HGFA and MET expression in mouse uterus changes during the estrous cycle in a stage-, cell type- and compartment-specific manner under the influence of estrogen and progesterone. HGF likely plays a role in cyclic endometrial remodeling such as cell proliferation via autocrine/paracrine mechanisms in mouse uterus.

Hum Reprod. 2010 Feb 10. [Epub ahead of print]

Association between phthalate exposure and glutathione S-transferase M1 polymorphism in adenomyosis, leiomyoma and endometriosis.

Huang PC, Tsai EM, Li WF, Liao PC, Chung MC, Wang YH, Wang SL.

Division of Environmental Health and Occupational Medicine, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.

BACKGROUND Phthalates are known to have estrogenic effects in cell models and experimental animals. However, the evidence regarding the effects of phthalates on human reproduction is still limited. We conducted a case-control study to determine whether estrogen-dependent diseases are associated with phthalate exposure and how the glutathione S-transferase M1 (GSTM1; a major detoxification enzyme) genotype modulates the risk. METHODS We recruited subjects who underwent laparotomy and had pathologic confirmation of endometriosis (EN) (n = 28), adenomyosis (AD) (n = 16) and leiomyoma (LEI) (n = 36) from the Department of Obstetrics and Gynecology at a medical center in Taiwan between 2005 and 2007. Controls (n = 29) were patients without any of the three aforementioned gynecologic conditions. Urine samples were collected before surgery and analyzed for seven phthalate metabolites using liquid chromatography-tandem mass spectrometry. Peripheral lymphocytes were used for GSTM1 genotype determination. RESULTS Patients with LEIs had significantly higher levels of total urinary mono-ethylhexyl phthalate (SigmaMEHP; 52.1 versus 18.9 microg/g creatinine, P < 0.05) than the controls, whereas patients with EN had an increased level of urinary mono-n-butyl phthalate (94.1 versus 58.0 microg/g creatinine, P < 0.05). Subjects with GSTM1 null genotype had significantly increased odds for AD relative to those with GSTM1 wild genotype [odds ratio (OR) = 5.30; 95% CI, 1.22-23.1], even after adjustment for age and phthalate exposure. Subjects who carried the GSTM1 null genotype and had a high urinary level of SigmaMEHP showed a significantly increased risk for AD (OR = 10.4; 95% CI, 1.26-85.0) and LEIs (OR = 5.93; 95% CI, 1.10-31.9) after adjustment for age, compared with those with GSTM1 wild-type and low urinary level of SigmaMEHP. CONCLUSIONS These results suggest that both GSTM1 null and phthalate exposure are associated with AD and LEI. Larger studies are warranted to investigate potential interaction between GSTM1 null and phthalate exposure in the etiology of estrogen-dependent gynecologic conditions.

Am J Reprod Immunol. 2010 Feb 8. [Epub ahead of print]

Differences in the Soluble HLA-G Blood Serum Concentration Levels in Patients with Ovarian Cancer and Ovarian and Deep Endometriosis.

Mach P, Blecharz P, Basta P, Marianowski P, Skret-Magierlo J, Kojs Z, Grabiec M, Wicherek L.

Department of Gynecology, Obstetrics and Oncology of the Jagiellonian University, Krakow, Poland.

Citation Mach P, Blecharz P, Basta P, Marianowski P, Skret-Magierlo J, Kojs Z, Grabiec M, Wicherek L. Differences in the soluble HLA-G blood serum concentration levels in patients with ovarian cancer and ovarian and deep endometriosis. Am J Reprod Immunol 2010 Problem The relationship between endometriosis and cancer has been widely discussed in the literature but is still not well clarified. Perhaps significantly, soluble human leukocyte antigen-G (sHLA-G) has been identified in the microenvironment of both ovarian cancer and endometrioma. The aim of this study has been to evaluate the sHLA-G levels in the blood sera of women with deep endometriosis and ovarian endometrioma over the course of the menstrual cycle and to compare to the levels of sHLA-G in the blood sera of women with ovarian cancer. Method of study In our study, we examined the blood sera obtained from 123 patients operated on because of ovarian cancer (65 cases), ovarian endometrioma (30 cases), and deep endometriosis (28 cases). We decided to compare the levels of sHLA-G in patients with endometriosis to those found in patients with ovarian cancer with respect to the menstrual cycle phases. The sHLA-G concentration level was measured by enzyme-linked immunosorbent assay kit. Results The level of sHLA-G concentration in the blood serum of patients with deep endometriosis fluctuates over the course of the menstrual cycle, and during the proliferative and secretory phases, it remains at a high level comparable to that found in patients with ovarian cancer. By contrast, the level of sHLA-G concentration in the blood serum of patients with ovarian endometrioma fluctuates minimally over the course of the different menstrual cycle phases and, as in patients with ovarian cancer, it remains at high level during the proliferative phase. Conclusion sHLA-G blood serum concentration levels would seem to provide important information regarding the degree of immune system regulation disturbance in both ectopic endometrial cells and the cancer cell suppressive microenvironment.

J Obstet Gynaecol. 2010 Feb;30(2):184-6.

Endometriosis-associated Lyme disease.

Matalliotakis IM, Cakmak H, Ziogos MD, Kalogeraki A, Kappou D, Arici A.

Department of Obstetrics and Gynecology, University of Crete, Heraklion, Crete, Greece. matakgr@yahoo.com

The aim of this study is to report three cases of patients with endometriosis and infertility, and associated with Lyme disease. The medical files of 405 women with endometriosis and 200 without endometriosis were studied retrospectively. We report 3 cases with endometriosis and Lyme disease. Of 405 patients with endometriosis treated in our study over a 6-year period, 3(0.8%) had Lyme disease. All cases presented with typical erythema migraines, fever and fatigue. The serological findings were positive for Borrelia burgdorferi, for 3 cases. Two out of 3 women underwent IVF-ET procedures and one of them conceived in the first cycle without complication during pregnancy or after childbirth recorded. We concluded that women with endometriosis are more likely to have chronic fatigue syndrome, systemic lupus erythematous, Sjögren’s syndrome, rheumatoid arthritis, multiple sclerosis, and other autoimmune inflammatory and endocrine diseases. A review of the literature confirms the uniqueness of the co-existence of Lyme disease in women with endometriosis in these cases.

J Coll Physicians Surg Pak. 2010 Jan;20(1):60-1.

Abdominal wall endometriosis.

Raza S, Maqsood R, Siddiqi HA.

Department of Radiology, PAF Hospital, Islamabad. ssrnaqvi@hotmail.com

Abdominal wall endometriosis is a rare condition, which usually develops in a surgical scar of abdominal hysterectomy or Caesarean section. A 38-year-old lady presented in the surgical out patient department complaining of painful swelling in the lower abdomen, at the left edge of the scar of caesarean section. Computerized tomographic (CT) scanning of the pelvis with contrast revealed an enhancing mass in the abdominal wall extending from the skin to the muscle layer. A diagnosis of a tumour or an inflammatory mass was suggested and fine needle aspiration cytology (FNAC) of the lesion was advised to ascertain the nature of the lesion. The mass was removed completely and histopathology of the surgical specimen revealed endometriosis.

Kyobu Geka. 2010 Feb;63(2):152-5.

Catamenial pneumothorax; report of a case.

[Article in Japanese]

Sugisawa C, Inaba H, Suzuki K, Hoshino Y, Shintani T, Shiraishi K, Nakayama T, Nishiumi T, Mori S, Isobe K.

Department of Surgery, Shizuoka Red Cross Hospital, Shizuoka, Japan.

A 40-year-old female had right-sided pneumothorax. She was treated with a chest tube. On the 2nd day, her menstruation started. Because of a persistent air leak, she underwent a thoracoscopic operation on the 15th day. During the operation, we noted a pulmonary bulla at the apex and multiple blue berry spots both on the visceral pleura and the tendinous part of the diaphragm. We performed a resection of the pulmonary bulla, partial diaphragmatic excision plus suture. Section of visceral pleura and diaphragm shows ductal structures, which is insistent with endometriosis. The serum CA125 level decreased to 39 U/ml. Following surgery, oral contraceptives was started and no recurrence was encountered thereafter.

Wiad Lek. 2009;62(2):129-34.

Health-related quality of life in women with endometriosis.

[Article in Polish]

Szpak R, Bugała-Szpak J, Drosdzol A, Skrzypulec V.

Katedra Zdrowia Kobiety, Wydział Opieki Zdrowotnej, Slaski Uniwersytet Medyczny w Katowicach. rafalszpak@op.pl

According to definition, endometriosis is a chronic gynaecological disease which results from ectopic location of the endometrium outside the uterine cavity. On the basis of various researches it is estimated that prevalence of endometriosis in the general population is 10% and the disease concerns women mainly in reproductive age. As an effect of the disease, following common gynaecological and psychiatric symptoms appear: chronic pelvic pain which occurs in different circumstances, depressive and anxiety disturbances. In relation to pathological changes, decrease of health-related quality of life (QOL) is observed. The topic of medical researches concerns frequently an influence of pharmacological and surgical treatment on QOL improvement in women with endometriosis. To achieve objective results in evaluation of quality of life, it is recommended to use standardized and validated questionnaires, such as EHP-30, EHP-5, SF-36, WHOQOF-100 or WHOQOL-BREF.

J Reprod Immunol. 2010 Mar;84(2):193-198. Epub 2010 Feb 4.

Effect of vascular endothelial growth factor and interleukin-1beta on apoptosis in endometrial cell cultures from patients with endometriosis and controls.

Bilotas M, Meresman G, Buquet R, Sueldo C, Barañao RI.

Instituto de Biología y Medicina Experimental (IBYME), Vuelta de Obligado 2490, C1428ADN Buenos Aires, Argentina.

The aim of this study was to evaluate the effect of vascular endothelial growth factor (VEGF) and interleukin-1beta (IL-1beta) on apoptosis induced by leuprolide acetate (LA) in endometrial epithelial cell cultures from patients with endometriosis. Primary endometrial epithelial cell cultures were obtained from uterine endometrial biopsies of patients with endometriosis and control women. Endometrial epithelial cells were incubated with LA; a combination of LA and VEGF; a combination of LA and IL-1beta; or in basal conditions. LA was added 3h prior to addition of VEGF and IL-1beta. After stimulation, the percentage of apoptotic cells was evaluated by the acridine orange-ethidium bromide technique and Bax expression was assessed by western blot. Treatment with LA enhanced the percentage of apoptotic cells in endometrial epithelial cells from subjects with endometriosis and control subjects. Addition of either VEGF or IL-1beta after exposure to LA restored the percentage of apoptotic cells to basal levels. Moreover, treatment with LA increased Bax expression in endometrial epithelial cells from patients with endometriosis. This effect was reverted by the addition of either VEGF or IL-1beta. Our results show that VEGF and IL-1beta reduce apoptosis and decrease Bax expression in endometrial epithelial cells from patients with endometriosis. This study suggests that VEGF and IL-1beta may protect endometriotic cells from undergoing apoptosis in addition to exerting their pro-angiogenic role. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Fertil Steril. 2010 Feb 3. [Epub ahead of print]

Inhibition of cell proliferation, adhesion, and invasion with an anti-L1-cell adhesion molecule monoclonal antibody in an in vitro endometriosis model.

Agic A, von Wussow U, Starzinski-Powitz A, Diedrich K, Altevogt P, Hornung D.

Department of Obstetrics and Gynecology, University of Schleswig-Holstein, Campus Luebeck.

The use of anti-L1-cell adhesion molecule monoclonal antibodies (anti-L1CAM-mAb) in an endometriosis epithelial cell line Z12 led to a statistically significant decrease in cell proliferation and cell invasion and to an inhibition of the adhesion compared with unspecific IgG-Ab treated and untreated cells. Because it increases the cell invasion and adhesion which consequently aggravates the disease, L1 could possibly promote endometriosis development; thus, further studies should evaluate the possible use of anti-L1-mAb in an animal endometriosis model. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Hum Reprod. 2010 Feb 3. [Epub ahead of print]

The effects of metformin and letrozole on endometriosis and comparison of the two treatment agents in a rat model.

Oner G, Ozcelik B, Ozgun MT, Serin IS, Ozturk F, Basbug M.

Department Obstetrics and Gynecology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.

BACKGROUND Our aim was to investigate the effects of metformin and letrozole on experimentally induced endometriosis in a rat model. METHODS Endometriotic implants were surgically formed, and 38 rats were randomly divided into four groups. Group 1 (control group, 8 rats) was given no medication. Group 2 (metformin group, 10 rats) was given 100 mg/kg/day of oral metformin. Group 3 (metformin group, 10 rats) was given 200 mg/kg/day of oral metformin. Group 4 (letrozole group, 10 rats) was given 0.1 mg/kg/day of oral letrozole. All rats continued to receive the treatment for 4 weeks and then were sacrificed to assess the size of implants and scores of adhesions. The histopathologic scores of implants in excised endometriotic foci were examined by a pathologist. RESULTS The mean surface area of endometriotic implants was similar in all groups before the treatment. Although the area was not reduced in controls, it was found to be significantly reduced in all treatment groups (44.50 +/- 23.37, 5.90 +/- 2.37, 4.30 +/- 1.33, 6.90 +/- 3.72 mm(2), respectively; P < 0.05). The effect was comparable between the treatment groups. The histopathologic assessment revealed that the histopathologic score of implants was lowest after 100 mg/kg/day metformin. Additionally, metformin reduced the severity of adhesions. CONCLUSIONS Metformin and letrozole caused a statistically significant regression of endometriotic implants. The effects of metformin on endometriotic tissue were at least comparable to letrozole.

Am J Obstet Gynecol. 2010 Feb 2. [Epub ahead of print]

Inpatient hospitalization for gynecologic disorders in the United States.

Whiteman MK, Kuklina E, Jamieson DJ, Hillis SD, Marchbanks PA.

Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, GA.

OBJECTIVE: The purpose of this study was to examine trends in hospitalizations for gynecologic disorders in the United States. STUDY DESIGN: Data on hospitalizations from 1998-2005 among women 15-54 years old were from the Nationwide Inpatient Sample, a nationally representative survey of inpatient hospitalizations. Hospitalizations with a principal diagnosis of a gynecologic disorder were used to estimate rates per 10,000 women. RESULTS: Gynecologic disorders accounted for 7% and 14% of all hospitalizations among women 15-44 and 45-54 years old, respectively. The most common diagnoses were uterine leiomyomas (rate = 27.5), menstrual disorders (rate = 12.3), endometriosis (rate = 9.5), genital prolapse (rate = 7.0), benign ovarian cysts (rate = 6.5), and pelvic inflammatory disease (rate = 6.1). The hospitalization rate for menstrual disorders increased from 9.8 in 1998 to 13.3 in 2005 (P-trend < .001). In contrast, rates declined for pelvic inflammatory disease, genital prolapse, benign ovarian cysts, and endometriosis (P-trend < .05) and were unchanged for uterine leiomyoma. CONCLUSION: Gynecologic disorders are an important contributor to inpatient hospitalization among women in the United States. Published by Mosby, Inc.

Eur J Pharm Sci. 2010 Feb 2. [Epub ahead of print]

A novel mifepristone-loaded implant for long-term treatment of endometriosis: In vitro and in vivo studies.

Mei L, Bao J, Tang L, Zhang C, Wang H, Sun L, Ma G, Huang L, Yang J, Zhang L, Liu K, Song C, Sun H.

Institute of Biomedical Engineering, Peking Union Medical College & Chinese Academy of Medical Sciences, The Tianjin Key Laboratory of Biomaterial Research, 236 Baidi Road, Nankai District, Tianjin 300192, China; College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116027, China; Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing 100084, PR China; The Shenzhen Key Lab of Gene and Antibody Therapy, Center for Biotech and Bio-Medicine and Division of Life Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, Guangdong 518055, China.

The objective of this study was to prepare a novel mifepristone-loaded PCL/Pluronic F68 implant to achieve long-term treatment of endometriosis. PCL/Pluronic F68 compound (90/10, w/w) with viscosity average molecular weight of 65,000 was successfully synthesized. The end-capped Pluronic F68 was incorporated in PCL matrixes as molecular dispersion without forming a copolymer. The mifepristone-loaded implant made of PCL/Pluronic F68 compound was a cylindrical capsule with an outer diameter of 2.5mm and an inner diameter of 2.2mm. The surface of PCL/Pluronic F68 compound appears porous because Pluronic F68 which is water soluble could leach out due to the water phase. Drug loading of 0.75-, 1.5- and 3.0-cm length implants was 3.05+/-0.18, 6.06+/-0.41 and 11.87+/-0.39mg, respectively. A sustained mifepristone release rate without obvious initial burst and later decline over a period of 180d was observed. The cumulative drug release showed a linear relationship with time, indicating that mifepristone release from the implants followed zero-order kinetics (R(2)>0.99). The data showed that the C(max) and AUC(0-inf) were proportional to imlant length and dose, and all groups reached plasma C(max) at about the same time (approximately 7d) and had similar T(1/2) (approximately 150d) and MRT (approximately 220d). There were obvious inhibitory effects on the growth of endometrial explants in Wister rats in a dose-dependent manner after administration of mifepristone-loaded implants with implant length from 1.5 to 9.0cm for 1-3 months. However, mifepristone-loaded implants with implant length of 12.0cm had no better inhibitory effects on the growth of endometrium when compared with the implants with implant length of 9.0cm (P>0.05). In conclusion, subcutaneous implantation of mifepristone-loaded PCL/Pluronic F68 capsules was proven an effective means for long-term treatment of chronic endometriosis. Copyright © 2010 Elsevier B.V. All rights reserved.

J Am Acad Nurse Pract. 2010 Feb;22(2):109-16.

Diagnosis and management of endometriosis: the role of the advanced practice nurse in primary care.

Mao AJ, Anastasi JK.

Columbia University School of Nursing, New York, New York 10032, USA. ajm2111@columbia.edu

PURPOSE: To discuss the etiology, clinical presentation, diagnosis, and management of endometriosis for the advanced practice nurse (APN) in primary care. DATA SOURCES: Selected research, clinical studies, clinical practice guidelines, and review articles. CONCLUSIONS: Commonly encountered by the APN in primary care, endometriosis is a chronic, progressive inflammatory disease characterized by endometrial lesions, cysts, fibrosis, or adhesions in the pelvic cavity, causing chronic pelvic pain and infertility in women of reproductive age. Because of its frequently normal physical examination findings, variable clinical presentations, and nonspecific, overlapping symptoms with other conditions, endometriosis can be difficult to diagnose. As there currently are no accurate noninvasive diagnostic tests specific for endometriosis, it is imperative for the APN to become knowledgeable about the etiology, clinical presentation, diagnosis, and current treatment options of this disease. IMPLICATIONS FOR PRACTICE: The APN in primary care plays an essential role in health promotion through disease management and infertility prevention by providing support and much needed information to the patient with endometriosis. APNs can also facilitate quality of care and manage treatments effectively to improve quality of life, reduce pain, and prevent further progression of disease. Practice recommendations include timely diagnosis, pain management, infertility counseling, patient education, and support for quality of life issues.

Am J Reprod Immunol. 2010 Feb 3. [Epub ahead of print]

Serum Anti-endometrial Antibodies in Infertile Women – Potential Risk Factor for Implantation Failure.

Sarapik A, Haller-Kikkatalo K, Utt M, Teesalu K, Salumets A, Uibo R.

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

Citation Sarapik A, Haller-Kikkatalo K, Utt M, Teesalu K, Salumets A, Uibo R. Serum anti-endometrial antibodies in infertile women – potential risk factor for implantation failure. Am J Reprod Immunol 2010 Problem Female infertility patients with diverse etiologies show increased production of autoantibodies. Method of study Immunoblot analysis of sera from patients with endometriosis and tubal factor infertility (TFI) and mass spectrometry identification of candidate antigens. Results The immunoblot results demonstrated the presence of IgA and IgG anti-endometrial antibodies (AEA) to various antigens at molecular weights ranging from 10 to 200 kDa. Differences were detected in certain AEA reactions between the patients’ groups and particular AEA were associated with in vitro fertilization (IVF) implantation failure. IgA AEA to a 47-kDa protein were more prevalent in TFI patients and were associated with unsuccessful IVF treatment. This antigen was subsequently identified as alpha-enolase. Conclusion Determination of the presence and spectra of AEA in patients with endometriosis and TFI undergoing IVF may be a useful marker to predict their pregnancy outcome.

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