Bioorg Med Chem. 2010 Jul 15;18(14):5157-71. Epub 2010 Jun 1.

2-acylamino-4,6-diphenylpyridine derivatives as novel GPR54 antagonists with good brain exposure and in vivo efficacy for plasma LH level in male rats.

Kobayashi T, Sasaki S, Tomita N, Fukui S, Nakayama M, Kiba A, Kusaka M, Matsumoto S, Yamaguchi M, Itoh F, Baba A.

Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd, 10 Wadai, Tsukuba-shi, Ibaraki 300-4293, Japan. Kobayashi_Toshitake@takeda.co.jp

GPR54 is a G protein-coupled receptor (GPCR) which was formerly an orphan receptor. Recent functional study of GPR54 revealed that the receptor plays an essential role to modulate sex-hormones including GnRH. Thus, antagonists of GPR54 are expected to be novel drugs for sex-hormone dependent diseases such as prostate cancer or endometriosis. We recently reported 2-acylamino-4,6-diphenylpyridines as the first small molecule GPR54 antagonists with high potency. However, the representative compound 1 showed low brain exposure, where GPR54 acts as a modulator of gonadotropins by binding with its endogenous ligand, metastin. In order to discover compounds that have not only potent GPR54 antagonistic activity but also good brain permeability, we focused on converting the primary amine on the side chain to a secondary or tertiary amine, and finally we identified 15a containing a piperazine group. This compound exhibited high affinity to human and rat GPR54, apparent antagonistic activity, and high brain exposure. In addition, intravenous administration of 15a to castrated male rat suppressed plasma LH level, which indicates the possibility of a small molecule GPR54 antagonist as a novel drug for sex-hormone dependent diseases. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

J Minim Invasive Gynecol. 2010 Jun 25. [Epub ahead of print]

Gynecologic Evaluation of Catamenial Pneumothorax Associated with Endometriosis.

Kumakiri J, Kumakiri Y, Miyamoto H, Kikuchi I, Arakawa A, Kitade M, Takeda S.

Departments of Obstetrics and Gynecology (Drs. J. Kumakiri, Y. Kumakiri, Kikuchi, Kitade, and Takeda), Respiratory Surgery (Dr. Miyamoto), and Human Pathology (Dr. Arakawa), Juntendo University School of Medicine, Tokyo, Japan.

STUDY OBJECTIVE: To assess the pathogenesis of catamenial pneumothorax associated with endometriosis from a gynecologic perspective. DESIGN: Retrospective study (Canadian Task Force classification II-2). SETTING: University hospital. PATIENTS: Eleven patients with clinically suspected catamenial pneumothorax due to frequently recurrent pneumothorax who underwent thoracoscopy between September 2003 and February 2007 at our hospital. INTERVENTION: Video-assisted thoracoscopy. MEASUREMENTS AND MAIN RESULTS: Episodes of pneumothorax, coexistence of intrapelvic endometriosis, classification of intrathoracic lesions according to the appearance of pelvic endometriosis using the revised American Society of Reproductive Medicine (re-ASRM) classification, and histopathologic findings in intrathoracic specimens were assessed. A total of 38 episodes of pneumothorax, all on the right side, were documented in 11 patients with catamenial pneumothorax. Median (range) patient age at the initial pneumothorax was 42 (29-47) years. The re-ASRM score in 6 patients in whom pelvic endometriosis was directly observed at laparoscopy and laparotomy was 56 (18-96). We postoperatively reviewed videotape recordings of video-assisted thoracoscopy, and observed superficial thoracic diaphragmatic lesions classified as red (n = 5), black (n = 8), and white (n = 9) with fenestration according to the re-ASRM classifications for pelvic endometriosis. Tissue associated with endometriosis was detected at histopathologic analysis of resected diaphragmatic lesions in 9 patients. No endometriosis was identified at histopathologic analysis of visceral pleural lesions in 7 patients who underwent lung resection. CONCLUSIONS: Gynecologic evaluation of catamenial pneumothorax associated with endometriosis is crucial to clarify the unelucidated pathogenesis of the disease. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.

Gynecol Obstet Fertil. 2010 Jul-Aug;38(7-8):490-5. Epub 2010 Jun 25.

Surgical treatment of tubo-ovarian abscess occurring in deep endometriosis.

[Article in French]

Mokdad C, Rozsnayi F, Delaunay F, Gregorczyk V, Auber M, Puscasiu L, Marpeau L, Roman H.

Clinique gynécologique et obstétricale, CHU Charles-Nicolle, Rouen, France.

Tubo-ovarian abscesses are likely to occur in women suffering from deep endometriosis. The aim of surgical management of tubo-ovarian abscesses is the laparoscopic drainage, while deep endometriosis resection should be delayed. Laparoscopic procedure carried out in emergency does not attempt at the excision of deep endometriotic lesions, and must avoid the choice of the laparoconversion, in order to avoid further changes in the pelvic anatomy rendering more difficult a curative surgery. We report six cases of patients presenting tubo-ovarian abscesses arising on deep endometriosis, and we discuss the choice of the 2-step surgical management. In four cases, deep endometriosis resection has been performed by laparoscopic route few months after the drainage of abscess and provided macroscopically complete excision of the disease. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Gynecol Obstet Fertil. 2010 Jul-Aug;38(7-8):442-6. Epub 2010 Jun 25.

Neurotrophins and pain in endometriosis.

[Article in French]

Borghese B, Vaiman D, Mondon F, Mbaye M, Anaf V, Noël JC, de Ziegler D, Chapron C.

Institut Cochin, CNRS (UMR 8104), université Paris Descartes, Paris, France. bruno.borghese@inserm.fr

OBJECTIVES: To evaluate the expression of five members of the neurotrophins family in ovarian endometriotic cyst (endometrioma) (OMA), compared to eutopic endometrium (EE) and to examine the correlation between the levels of induction and the pain intensity. PATIENTS AND METHODS: Twelve Caucasian women in luteal phase, operated for painful stage IV endometriosis were assigned to 2 groups according to a total Visual Analog Scale (tVAS) score above 15 or below 10. tVAS takes into account all VAS scores for dysmenorrhea, deep dyspareunia, non cyclic chronic pelvic pain, gastrointestinal and lower urinary symptoms. Samples of OMA and EE were processed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for NGF, BDNF, NT-3, NT-4/5 and NTRK2 mRNA expression. Expression levels in OMA were compared to those in EE on one hand and between two groups of 6 mild painful and 6 highly painful patients on the other. RESULTS: All neurotrophins were significantly higher expressed in OMA than in EE, in particular NGF and BDNF (induction ratios: 20.6 and 9.7, respectively). In contrast, no correlation was observed between induction ratios and pain intensity. CONCLUSION AND DISCUSSION: This is the first study reporting an over-expression of all neurotrophins in endometriosis, as only NGF was previously documented. It confirms the central role of this family in the genesis and modulation of pain in endometriosis. Anti-neurotrophin selective therapy might be a promising way of analgesia in the future. Copyright 2010 Elsevier Masson SAS. All rights reserved.

Fertil Steril. 2010 Aug;94(3):e52. Epub 2010 Jun 25.

Reply of the Authors: Comparing high-sensitivity C-reactive protein (hs-CRP) with CRP as a soluble serum marker for the diagnosis of women with endometriosis.

Lermann J, Mueller A, Körber F, Oppelt P, Beckmann MW, Deitrich R, Renner SP.

University Hospital Erlangen, Department of Obestetrics and Gynecology, Erlangen, Germany.

Fertil Steril. 2010 Aug;94(3):e51; author reply e52. Epub 2010 Jun 25.

Comparing high-sensitivity C-reactive protein (hs-CRP) with CRP as a soluble serum marker for the diagnosis of women with endometriosis.

Verit FF, Hilali NG.

Comment on:

Fertil Steril. 2010 Jun 23. [Epub ahead of print]

Aromatase inhibitors in recurrent ovarian endometriomas: report of five cases with literature review.

Seal SL, Kamilya G, Mukherji J, De A, Ghosh D, Majhi AK.

Department of Obstetrics and Gynecology, Bankura Sammilani Medical College, Gobindanagar, West Bengal.

OBJECTIVE: To determine the role of the aromatase inhibitor letrozole in the treatment of recurrent ovarian endometrioma cases. DESIGN: Nonrandomized proof of concept study. SETTINGS: Outpatient tertiary-care center. PATIENT(S): Five premenopausal patients with documented ovarian endometriomas and chronic pelvic pain, all of whome were previously treated with surgery and medicine with unsatisfactory results. INTERVENTION(S): Ovarian endometriomas were diagnosed by biopsy after laparoscopic ovarian cystectomy and subsequently treated with hormomes. After a 6-month washout of endometriosis hormone therapies, women took letrozole (2.5 mg), one tablet of 0.15 mg of desogestrel, and 0.03 mg of ethinyl estradiol, calcium (1,200 mg), and vitamin D(3) (800 IU) daily for 6 months. MAIN OUTCOME MEASURE(S): Size of endometriomas (monitored by ultrasound), assessment of pelvic pain (by visual analog scale), and bone density (DEXA scan). RESULT(S): Disappearance of ovarian endometrioma and reduction in pelvic pain in all cases at the end of 6 months. The size of ovarian endometriomas was reduced after 3 months. Pain scores decreased only after 1 month of treatment and continued decreasing in each treatment month. Overall, no significant change in bone density was detected. CONCLUSION(S): Letrozole given with combined pills achieved complete regression of recurrent endometriotic cysts and pain relief in all cases. Copyright © 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

BMC Womens Health. 2010 Jun 25;10:22.

The LIFESTYLE study: costs and effects of a structured lifestyle program in overweight and obese subfertile women to reduce the need for fertility treatment and improve reproductive outcome. A randomised controlled trial.

Mutsaerts MA, Groen H, ter Bogt NC, Bolster JH, Land JA, Bemelmans WJ, Kuchenbecker WK, Hompes PG, Macklon NS, Stolk RP, van der Veen F, Maas JW, Klijn NF, Kaaijk EM, Oosterhuis GJ, Bouckaert PX, Schierbeek JM, van Kasteren YM, Nap AW, Broekmans FJ, Brinkhuis EA, Koks CA, Burggraaff JM, Blankhart AS, Perquin DA, Gerards MH, Mulder RJ, Gondrie ET, Mol BW, Hoek A.

Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. m.a.q.mutsaerts@og.umcg.nl

BACKGROUND: In the Netherlands, 30% of subfertile women are overweight or obese, and at present there is no agreement on fertility care for them. Data from observational and small intervention studies suggest that reduction of weight will increase the chances of conception, decrease pregnancy complications and improve perinatal outcome, but this has not been confirmed in randomised controlled trials. This study will assess the cost and effects of a six-months structured lifestyle program aiming at weight reduction followed by conventional fertility care (intervention group) as compared to conventional fertility care only (control group) in overweight and obese subfertile women. We hypothesize that the intervention will decrease the need for fertility treatment, diminish overweight-related pregnancy complications, and will improve perinatal outcome. METHODS/DESIGN: Multicenter randomised controlled trial in subfertile women (age 18-39 year) with a body mass index between 29 and 40 kg/m2. Exclusion criteria are azoospermia, use of donor semen, severe endometriosis, premature ovarian failure, endocrinopathies or pre-existent hypertensive disorders.In the intervention group the aim is a weight loss of at least 5% to10% in a six-month period, to be achieved by the combination of a diet, increase of physical activity and behavioural modification. After six months, in case no conception has been achieved, these patients will start fertility treatment according to the Dutch fertility guidelines. In the control group treatment will be started according to Dutch fertility guidelines, independently of the patient’s weight. OUTCOME MEASURES AND ANALYSIS: The primary outcome measure is a healthy singleton born after at least 37 weeks of gestation after vaginal delivery. Secondary outcome parameters including pregnancy outcome and complications, percentage of women needing fertility treatment, clinical and ongoing pregnancy rates, body weight, quality of life and costs.Data will be analysed according to the intention to treat principle, and cost-effectiveness analysis will be performed to compare the costs and health effects in the intervention and control group. DISCUSSION: The trial will provide evidence for costs and effects of a lifestyle intervention aiming at weight reduction in overweight and obese subfertile women and will offer guidance to clinicians for the treatment of these patients. TRIAL REGISTRATION: Dutch Trial Register NTR1530.

J Assist Reprod Genet. 2010 Jun 25. [Epub ahead of print]

Endometriosis and infertility.

Bulletti C, Coccia ME, Battistoni S, Borini A.

Physiopathology of Reproduction, Cattolica’s General Hospital and University of Bologna, “Polo Scientifico Didattico di Rimini”, Bologna, Italy, bulletticarlo@libero.it.

Endometriosis is a debilitating condition characterized by high recurrence rates. The etiology and pathogenesis remain unclear. Typically, endometriosis causes pain and infertility, although 20-25% of patients are asymptomatic. The principal aims of therapy include relief of symptoms, resolution of existing endometriotic implants, and prevention of new foci of ectopic endometrial tissue. Current therapeutic approaches are far from being curative; they focus on managing the clinical symptoms of the disease rather than fighting the disease. Specific combinations of medical, surgical, and psychological treatments can ameliorate the quality of life of women with endometriosis. The benefits of these treatments have not been entirely demonstrated, particularly in terms of expectations that women hold for their own lives. Although theoretically advantageous, there is no evidence that a combination medical-surgical treatment significantly enhances fertility, and it may unnecessarily delay further fertility therapy. Randomized controlled trials are required to demonstrate the efficacy of different treatments.

Biol Reprod. 2010 Jun 23. [Epub ahead of print]

Identification and Quantification of Dopamine Receptor 2 in Human Eutopic and Ectopic Endometrium: A Novel Molecular Target for Endometriosis Therapy.

Novella-Maestre E, Carda C, Ruiz-Sauri A, Garcia-Velasco JA, Simon C, Pellicer A.

Previous studies in an experimental mice model of endometriosis have shown that the dopamine agonist (DA) cabergoline (Cb2) reduces angiogenenesis and endometriotic lesions, hypothetically binding to the dopamine receptor type-2 (DRD2). To date, this has not been described in human endometrium and/or endometriotic lesions. Thus, we aimed to investigate the presence of DRD2 in said tissues. Endometrium fragments were implanted in nude mice treated with different doses of Cb2. PCR assays and immunohistochemistry were performed to analyze the gene and protein expression (respectively) of DRD2, VEGF and VEGF receptor-2 (KDR). In addition, lesions and endometrium from women with mild and severe endometriosis and endometrium from healthy women were collected to analyze their gene expression profile. In experimental endometriosis, DRD2 was expressed at gene and protein levels in all three groups. VEGF gene and protein expression were significantly lower in lesions treated with Cb2 than in controls. KDR protein expression was significantly lower in experimental lesions treated with Cb2 than in controls. In eutopic endometria, there was a significant decrease in DRD2 expression and an increase in VEGF in women with mild and severe endometriosis with respect to healthy patients. In endometriosis, KDR expression was significantly higher in red than in white and black lesions. VEGF expression was significantly lower in black than in red lesions. DRD2 is present in the human eutopic and ectopic endometrium and is regulated by DA, which provides the rationale for pilot studies to explore its use in the treatment of endometriosis.

N Engl J Med. 2010 Jun 24;362(25):2389-98.

Clinical practice. Endometriosis.

Giudice LC.

Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143-0132, USA. giudice@obgyn.ucsf.edu

BMJ. 2010 Jun 23;340:c2168. doi: 10.1136/bmj.c2168.

Endometriosis.

Engemise S, Gordon C, Konje JC.

Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester LE2 7LX.

Comment in:

Hum Reprod. 2010 Aug;25(8):2068-83. Epub 2010 Jun 23.

A conditionally replicative adenovirus, CRAd-S-pK7, can target endometriosis with a cell-killing effect.

Paupoo AA, Zhu ZB, Wang M, Rein DT, Starzinski-Powitz A, Curiel DT.

Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, AL, USA. A.A.V.Paupoo.96@cantab.net

BACKGROUND: Novel therapeutic approaches for endometriosis based on molecular strategies may prove to be useful. Conditionally replicative adenoviruses (CRAds) are designed to exploit key differences between target and normal cells. The wild-type adenovirus (Adwt) promoter can be replaced by tissue-specific promoters, allowing viral replication only in target cells. Viral infectivity can be enhanced by altering Ad tropism via fiber modification. We investigated whether CRAds can be used to target endometriosis and determined the most efficient transcriptional- and transductional-targeting strategy. METHODS: An in vitro study was carried out using human endometriotic cell lines, 11Z (epithelial) and 22B (stromal), normal human ovarian surface epithelial cell line (NOSE006) and primary human endometriosis cells. A total of 9 promoters and 12 Ad tropism modifications were screened by means of a luciferase reporter assay. From this screening data, three CRAds (CRAd-S-pK7, CRAd-S-RGD, CRAd-S-F5/3sigma1, all incorporating the survivin promoter but with different fiber modifications) were selected to perform experiments using Adwt and a replication-deficient virus as controls. CRAds were constructed using a plasmid recombination system. Viral-binding capacity, rates of entry and DNA replication were evaluated by quantitative real-time PCR of viral genome copy. Cell-killing effects were determined by crystal violet staining and a cell viability assay for different concentrations of viral particles per cell. RESULTS: Comparison of promoters demonstrated that the survivin promoter exhibited the highest induction in both endometriotic cell lines. Among the fiber-modified viruses, the polylysine modification (pK7) showed the best infection enhancement. CRAd-S-pK7 was validated as the optimal CRAd to target endometriosis in terms of binding ability, entry kinetics, DNA replication and cell-killing effect. CRAd-S-pK7 also exhibited a high level of DNA replication in primary endometriosis cells. CONCLUSIONS: CRAd-S-pK7 has the best infection and cell-killing effect in the context of endometriosis. It could prove to be a useful novel method to target refractory cases of endometriosis.

Orv Hetil. 2010 Jul 11;151(28):1137-44.

Current treatment of endometriosis with laparoscopic surgery.

[Article in Hungarian]

Berkes E, Bokor A, Rigó J Jr.

Semmelweis Egyetem, Altalános Orvostudományi Kar I. Szülészeti és Nogyógyászati Klinika Budapest. berkes.eniko@noi1.sote.hu

Surgical treatment of endometriosis aims to remove all visible areas of pelvic endometriosis and restore anatomy by division of adhesions, as well as relieve painful symptoms. In this paper, we summarize the advantages, disadvantages, and efficacy of different laparoscopic surgical procedures in the treatment of endometriosis-associated pelvic pain and infertility. Modern endometrial surgery primarily involves laparoscopy, while indication of previously widespread laparotomy has been restricted to special cases. Surgery for the treatment of peritoneal endometriosis includes several options: electrocoagulation, laser ablation, or excision of the lesions, all of which have similar efficacy in the therapy of endometriosis-associated pelvic pain and infertility. There are two effective techniques for treating ovarian endometrioma: excision (stripping) technique or ablation of the cyst wall. It has been conclusively proven that stripping provides a more favorable outcome than drainage and ablation with regard to alleviating pain symptoms and infertility. The treatment of deeply infiltrating endometriosis involves some of the most challenging dissections in endometrial surgery. Such deeply infiltrating lesions can be most securely removed with laser techniques. For example, rectovaginal septum endometriosis can be completely removed with laser therapy. In case of bowel endometriosis, the affected part of the bowel can be removed by segmental resection, disc resection, or superficial partial-thickness excision. In most cases segmental colorectal resection is employed, because it is the most effective treatment currently available. In case of slight ureteral endometriosis, laparoscopic ureterolysis can be an effective treatment option; however, with obstructive uropathy segmental resection and anastomosis are indicated. Laparoscopic uterosacral nerve ablation and praesacral neurectomy are ancillary procedures meant to further decrease endometriosis-associated pelvic pain symptoms. However, the efficacy of these techniques is not yet proven and currently they appear to offer no added benefits beyond those achievable with conservative surgery alone. The ever improving surgical techniques steadily increase the efficacy of the treatment of endometriosis-associated infertility and pelvic pain, as well as delay recurrence of the disease.

Eur J Surg Oncol. 2010 Jul;36(7):691-8. Epub 2010 Jun 8.

Neutrophil to lymphocyte ratio for preoperative diagnosis of uterine sarcomas: a case-matched comparison.

Kim HS, Han KH, Chung HH, Kim JW, Park NH, Song YS, Kang SB.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 28 Yeongun-Dong, Chongno-Gu, Seoul 110-744, Republic of Korea.

BACKGROUND: Uterine sarcomas are rare among all uterine malignancies, and frequently misdiagnosed as benign uterine diseases such as leiomyoma and adenomyosis because of lack of feasible tools for the preoperative diagnosis. Although some studies have suggested the role of serum CA-125 levels for the preoperative diagnosis, the efficacy is controversial. Since malignancy is known to be associated with systemic inflammation which leads to hematological alteration, we compared the efficacy for the preoperative diagnosis of uterine sarcomas between the neutrophil to lymphocyte ratio (NLR) and serum CA-125 levels using a case-match comparison. METHODS: From November 2004 to December 2008, 55 patients with carcinosarcoma (n=21), leiomyosarcoma (n=20) and endometrial stromal sarcoma (n=14) were matched to 330 patients with leiomyoma (n=165) and adenomyosis (n=165) in terms of age at diagnosis, body mass index and uterine volume. RESULTS: The receiver operating characteristic curve showed the best cut-off values of the NLR (>or=2.12) and serum CA-125 levels (>or=27.5U/ml) for the preoperative diagnosis of uterine sarcomas, demonstrating that the NLR was more powerful for the preoperative diagnosis of uterine sarcomas than serum CA-125 levels (sensitivity, 74.5% vs. 52.3%; specificity, 70.3% vs. 50.5%; positive predictive value, 29.5% vs. 15.1%; negative predictive value, 94.3% vs. 86.5%; accuracy, 60.6% vs. 49.6%; p<0.05). Furthermore, the NLR reflected recurrence and progression more accurately than serum CA-125 levels in patients with uterine sarcomas. CONCLUSIONS: These findings suggest that the NLR may be more useful than serum CA-125 levels as a cost-effective tool for the preoperative diagnosis in patients with uterine sarcomas.

Rev Esp Med Nucl. 2010 Jun 4. [Epub ahead of print]

Abdominal splenosis: An often underdiagnosed entity.

[Article in Spanish]

Vercher-Conejero JL, Bello-Arqués P, Pelegrí-Martínez L, Hervás-Benito I, Loaiza-Góngora JL, Falgas-Lacueva M, Ruiz-Llorca C, Pérez-Velasco R, Mateo-Navarro A.

Servicio de Medicina Nuclear, Hospital Universitario La Fe, Valencia, España.

Splenosis is defined as the heterotopic autotransplantation of splenic tissue because of a ruptured spleen due to trauma or surgery. It is a benign and incidental finding, although imaging tests may sometimes orient toward malignancy simulating renal tumors, abdominal lymphomas, endometriosis, among other. We report the case of a 42-year old male in whom a MRI was performed after a study due to abdominal pain. Multiple enlarged lymph nodes were observed in the abdomen, suggestive of lymphoproliferative disease. As an important background, splenectomy was carried out due to abdominal trauma at age 9. After several studies, it was decided to perform a (99m)Tc-labeled heat-damaged red blood cell scintigraphy that showed multiple pathological deposits distributed throughout the abdomen, and even the pelvis, being consistent with splenosis. Copyright © 2010 Elsevier España, S.L. y SEMNIM. All rights reserved.

J Obstet Gynaecol Can. 2010 Jun;32(6):598-608.

Adhesion prevention in gynaecological surgery.

[Article in English, French]

Robertson D, Lefebvre G, Leyland N, Wolfman W, Allaire C, Awadalla A, Best C, Contestabile E, Dunn S, Heywood M, Leroux N, Potestio F, Rittenberg D, Senikas V, Soucy R, Singh S.

Toronto ON.

OBJECTIVES: To review the etiology and incidence of and associative factors in the formation of adhesions following gynaecological surgery. To review evidence for the use of available means of adhesion prevention following gynaecological surgery. OPTIONS: Women undergoing pelvic surgery are at risk of developing abdominal and/or pelvic adhesive disease postoperatively. Surgical technique and commercial adhesion prevention systems may decrease the risk of postoperative adhesion formation. OUTCOMES: The outcomes measured are the incidence of postoperative adhesions, complications related to the formation of adhesions, and further intervention relative to adhesive disease. EVIDENCE: Medline, EMBASE, and The Cochrane Library were searched for articles published in English from 1990 to March 2009, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, cohort studies, and meta-analyses specifically addressing postoperative adhesions, adhesion prevention, and adhesive barriers. Searches were updated on a regular basis and incorporated in the guideline to March 2009. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care SUMMARY STATEMENTS: 1. Meticulous surgical technique is a means of preventing adhesions. This includes minimizing tissue trauma, achieving optimal hemostasis, minimizing the risk of infection, and avoiding contaminants (e.g., fecal matter) and the use of foreign materials (e.g., talcum powder) when possible. (II-2). 2. The risk of adhesions increases with the total number of abdominal and pelvic surgeries performed on one patient; every surgery needs to be carefully considered in this context. (II-2). 3. Polytetrafluoroethylene (Gore-Tex) barrier is more effective than no barrier or oxidized regenerated cellulose in preventing adhesion formation. (I). 4. Oxidized regenerated cellulose (Interceed) adhesion barrier is associated with a reduced incidence of pelvic adhesion formation at both laparoscopy and laparotomy when complete hemostasis is achieved. Oxidized regenerated cellulose may increase the risk of adhesions if optimal hemostasis is not achieved. (II-2). 5. Chemically modified sodium hyaluronate/carboxymethylcellulose (Seprafilm) is effective in preventing adhesion formation, especially following myomectomies. There is insufficient evidence on the effect of sodium hyaluronate/carboxymethylcellulose on long-term clinical outcomes such as fertility, chronic pelvic pain or small bowel obstruction. (II-2). 6. No adverse effects have been reported with the use of oxidized regenerated cellulose, polytetrafluoroethylene, or sodium hyaluronate/carboxymethylcellulose. (II-1). 7. Various pharmacological agents have been marketed as a means of preventing adhesions. None of these agents are presently available in Canada. There is insufficient evidence for the use of pharmacological agents in preventing adhesions. (III-C). RECOMMENDATIONS: 1. Surgeons should attempt to perform surgical procedures using the least invasive method possible in order to decrease the risk of adhesion formation. (II-1B ). When feasible, for example, a laparoscopic surgical approach is preferable to an abdominal approach, and a vaginal or laparoscopic hysterectomy is preferable to an abdominal hysterectomy. 2. Precautions should be taken at surgery to minimize tissue trauma in order to decrease the risk of postoperative adhesions. These precautions include limiting packing, crushing, and manipulating of tissues to what is strictly required for safe completion of the procedure. (III-B). 3. Surgeons could consider using an adhesion barrier for patients who are at high risk of forming clinically significant adhesions (i.e., patients who have endometriosis or pelvic inflammatory disease or who are undergoing a myomectomy). If there is a risk of ongoing bleeding from the surgical site, oxidized regenerated cellulose (Interceed) should not be used as it may increase the risk of adhesions in this situation. (II-2B).

Gynecol Endocrinol. 2010 Jun 23. [Epub ahead of print]

The expression of human leukocyte antigens class I and II in women with endometriosis or adenomyosis.

Baka S, Frangou-Plemenou M, Panagiotopoulou E, Makrakis E, Kaltsakas G, Hassiakos D, Kondi-Pafiti A.

Department of Biopathology, Aretaieion Hospital, University of Athens, Athens, Greece.

Objectives. The human leukocyte antigen (HLA) system has been implicated in the aetiology of endometriosis. We aimed to compare the HLA class I and II expression in endometrial specimens from women with endometriosis or adenomyosis. Methods. We studied the HLA class I and II expression in endometrial specimens from 16 women with endometriosis and 15 with adenomyosis which were compared with 15 specimens from women without endometriosis or adenomyosis. Immunohistochemistry was performed using mouse antihuman IgG2a monoclonal antibody for HLA I and IgG1 for HLA II. Results. Women with endometriosis had significantly higher HLA I and II expression in stroma (100% and 87.5% vs. 66.7% and 40%, p < 0.02 and p = 0.007, respectively) and glands (87.5% and 56.3% vs. 46.7% and 20%, p < 0.02 and p = 0.04, respectively) compared to controls, while in the adenomyosis group the expression of HLA I was comparable with controls and the HLA II expression was increased in stromal cells (73.3% vs. 40%, p = 0.03) and decreased in glands (6.6% vs. 20%, p = NS). Conclusion. Women with endometriosis had a significantly higher expression of HLA molecules whereas in adenomyosis there was a tendency of lower expression of these molecules. This could explain the suppression of cellular immunity in the peritoneal cavity.

Obstet Gynecol. 2010 Jul;116(1):223-36.

Practice bulletin no. 114: management of endometriosis.

[No authors listed]

Int J Gynecol Pathol. 2010 Jul;29(4):341-2.

Expression of COX-2 in intestinal endometriosis to: Tokyol C, et al. Int J Gynecol Pathol 2009;28:148-56.

Meinel A, Hentschel B, Horn LC.

Comment on:

Int J Gynecol Pathol. 2010 Jul;29(4):328-34.

Pure primary squamous cell carcinoma of the ovary: a report of two cases and review of the literature.

Park JY, Song JS, Choi G, Kim JH, Nam JH.

Department of Obstetrics and Gynecology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Pure primary squamous cell carcinoma (SCCa) of the ovary not associated with pre-existing ovarian lesions including dermoid cysts, Brenner tumors, or endometriosis is extremely rare. The last 2 types of SCCa and pure primary SCCa have been classified by the World Health Organization criteria as surface epithelial-stromal tumors. On account of the rarity of pure primary SCCa of the ovary, the clinical features and effective treatments have not been established. This study describes 2 such cases that we recently encountered in a review of the literature. The literature shows that patients with advanced-stage tumors have very poor survival outcomes, despite a combination of surgery, radiation therapy, and chemotherapy.

Rev Prat. 2010 May 20;60(5):603-5, 607-9.

Endometriosis.

[Article in French]

Daraï E, Bazot M, Ballester M.

Service de gynécologie-obstétrique, hôpital Tenon (AP-HP), université Pierre-et-Marie-Curie Paris-6, 75020 Paris Cedex. emile.darai@tnn.aphp.fr

Endometriosis is an estrogen-dependant disease that affects 10 to 15% of women of reproductive age. Its aetiology and molecular mechanisms involved have not yet been fully explored. Endometriosis is defined by the presence of endometrium-like tissue outside the uterus, primarily on the pelvic peritoneum and ovaries. The main clinical features are chronic pelvic pain, pain during intercourse, and infertility. Due to the limitations of clinical examination, additional explorations such as transvaginal sonography and magnetic resonance imaging are required to precise mapping of endometriotic lesions. Medical therapies based on progesterone and gonadotropin-releasing hormone agonists have a suspensive effect. In some cases, surgery is necessary and will be best achieved in specialized centers.

Phytother Res. 2010 Jun 17. [Epub ahead of print]

Antiangiogenic phytochemicals and medicinal herbs.

Jeong SJ, Koh W, Lee EO, Lee HJ, Lee HJ, Bae H, Lü J, Kim SH.

College of Oriental Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.

Medicinal herbs and their phytochemicals are potential novel leads for developing antiangiogenic drugs. This review aims to assess the current status of research with medicinal herbs and their phytochemicals for the development of antiangiogenic agents for cancer and other angiogenesis-related diseases including inflammation, diabetic retinopathy, endometriosis and obesity. Most studies reviewed have focused on vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR-2) signaling for endothelial response processes and have led to the identification of many potential antiangiogenic agents. Since human clinical trials with antiangiogenic modalities targeting VEGF/VEGFR-2 signaling have shown limited efficacy and occasional toxic side effects, screening strategies for herbal phytochemicals based on other signaling pathways important for cancer-endothelial and stromal crosstalks should be emphasized in the future. Copyright (c) 2010 John Wiley & Sons, Ltd.

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

Application of the nuclear factor-kappaB 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-kappaB inhibitor, showed stronger inhibitory effects on nuclear factor-kappaB 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-alpha-induced expressions of CD44s, matrix metalloproteinase-9, and vascular endothelial growth factor whereas reversed tumor necrosis factor-alpha-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.

Am J Reprod Immunol. 2010 Jun 17. [Epub ahead of print]

Association of Peroxisome Proliferator-Activated Receptor-Gamma 2 Pro12Ala Polymorphism with Advanced-Stage Endometriosis.

Hwang KR, Choi YM, Kim JM, Lee GH, Kim JJ, Chae SJ, Moon SY.

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

Citation Hwang KR, Choi YM, Kim JM, Lee GH, Kim JJ, Chae SJ, Moon SY. Association of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala polymorphism with advanced-stage endometriosis. Am J Reprod Immunol 2010 Problem To investigate whether the peroxisome proliferator-activated receptor (PPAR)-gamma2 Pro12Ala polymorphism is associated with a risk of advanced-stage endometriosis in a Korean population. Methods of study Case-control study in a collective of 446 patients and 427 controls. The Pro12Ala polymorphism of PPAR-gamma2 gene was genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Results The distribution of the PPAR-gamma2 Pro12Ala polymorphism was different between the advanced-stage endometriosis group and the control group (non-CC rates were 5.2% for patients with advanced endometriosis and 10.1% for the control group, respectively, P = 0.006). The frequency for the Ala-12 allele variant was significantly lower in patients with advanced stage of endometriosis (2.7%) than in the control group (5.3%) (P = 0.006). Conclusion These findings suggest that the PPAR-gamma2 Pro12Ala polymorphism is associated with advanced-stage endometriosis in the Korean population. Unlike results from other studies reported so far, the Ala-12 allele may have protective effects against advanced-stage endometriosis in the Korean population.

Gynecol Obstet Invest. 2010 Jun 16;70(3):154-159. [Epub ahead of print]

Reproductive Health Characteristics of Urban South Korean Women.

Lee DY, Koo YA, Yoon BK, Choi D.

Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, Korea.

Aims: To characterize the reproductive health of urban South Korean women of reproductive age. Methods: A cross-sectional online survey on menstrual patterns, sexual behavior, utilization of contraception, and perception of gynecological diseases was administered to 500 women from 15 to 39 years of age in five major cities of South Korea. Results: Among the respondents, 76.8 and 25% experienced dysmenorrhea and abnormal uterine bleeding, respectively. Two-thirds of the respondents with dysmenorrhea used analgesics. After analgesics, herbal medicine was the next most commonly used treatment. The mean age of first sexual intercourse was 24.3 years, and 68.8% of the sexually active women used contraception. The most commonly used contraceptive method was the condom (79.7%), and many women (up to 62.2%) demonstrated a distorted understanding of oral contraceptives. Although many women were aware of general gynecological diseases such as cervical cancer (77%), endometriosis (64.4%), and leiomyoma (62.6%), only 22.2% of the respondents had visited a clinic for a gynecological examination, and among those who had visited a clinic, the main reason for the visit was pregnancy (44.1%). Conclusion: The results of this survey provide insight into and allow us to characterize the reproductive health status of urban South Korean women. Copyright © 2010 S. Karger AG, Basel.

In Vivo. 2010 May-Jun;24(3):297-301.

Genetic variants of vascular endothelial growth factor and risk for the development of endometriosis.

Attar R, Agachan B, Kuran SB, Toptas B, Eraltan IY, Attar E, Isbir T.

Department of Obstetrics and Gynecology, Teditepe University Hospital, Istanbul, Turkey.

BACKROUND/AIMS: Endometriosis is regarded as a complex disese, in which genetic and environmental factors contribute to the disease phenotype. Whether vascular endothelial growth factor (VEGF) -460 C/T and +405 G/C polymorphisms are associated with susceptibility to endometriosis was investigated. PATIENTS AND METHODS: Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. Sixty out of the 112 women enrolled had no endometriosis, 11 had mild or early-stage endometriosis and 41 had severe endometriosis. Polymerase chain reaction (PCR), restriction fragment length polymorphism and agarose gel electrophoresis techniques were used to determine the -460 C/T and +405 G/C genotypes. RESULTS: The VEGF +405 G/C genotype frequencies among the cases and controls were CC 55.8% and 35%; GC 30.8% and 50.0%; GG 13.5% and 15.0%, respectively. The allelic frequencies were C 71.15% (cases) and 60.0% (controls) and G 28.8% (cases) and 40% (controls). Patients with endometriosis had a higher incidence of the VEGF +405 CC genotype compared with the controls (p=0.027). Women with VEGF +405 CC genotype had 2.3-fold higher risk for endometriosis. VEGF +405 GC genotype and G allele in the control group was higher than the endometriosis group (p=0.039, p=0.027 respectively). The VEGF -460 C/T genotype frequencies among the cases were CC 21.2%, CT 26.9% and TT 51.9%; the C and T allelic frequencies were 34.6% and 65.3%, respectively. The VEGF -460 genotype frequencies among the controls were CC 31.70%, CT 18.3% and TT 50.0%; the C and T allelic frequencies were 40.8% and 59.1%, respectively (p>0.05). There was linkage disequilibrium between VEGF -460 C/T and +405 G/C polymorphisms (D’: 0.197, r(2)=0.013). We observed that the VEGF 460T/405C haplotype frequency was significantly higher in patients compared to controls (p=0.011). CONCLUSION: Our data suggest that the CC genotype of VEGF +405 and 460T/405C haplotypes of VEGF may be associated with the risk of endometriosis, but the G allele of VEGF +405 appears to be protective against endometriosis.

Int J Gynaecol Obstet. 2010 Sep;110(3):208-212. Epub 2010 May 31.

Increased basal FSH levels as predictors of low-quality follicles in infertile women with endometriosis.

de Carvalho BR, Rosa-E-Silva AC, Rosa-E-Silva JC, Reis RM, Ferriani RA, Silva-de-Sá MF.

Service of Human Reproduction, Department of Gynecology and Obstetrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

OBJECTIVE: To determine whether basal levels of follicle-stimulating hormone (FSH) and anti-müllerian hormone (AMH), antral follicle count (AFC), and the numbers of dominant follicles, oocytes, and mature oocytes retrieved after ovarian stimulation differed between infertile women with endometriosis and healthy women undergoing assisted reproduction techniques (ART). METHOD: Of 77 consecutive ART candidates, 27 were infertile and had endometriosis. A male factor caused the infertility of the other 50, who acted as controls. RESULTS: The AMH and AFC levels were similar in the 2 groups. The FSH levels were higher (8.28mIU/mL [range, 5.25-24.1mIU/mL] vs 5.91mIU/mL [range, 2.47-18.7mIU/mL]; P<0.01) in the study group. And the numbers of retrieved (n=5 [range, 0-12] vs n=9 [range, 0-27; P<0.05) and mature oocytes (n=4 [range, 0-11] vs n=5 [range, 0-16]; P<0.05) were less in the study group. CONCLUSION: Because AMH levels were unchanged, endometriosis seems not to damage the primordial pool of follicles and oocytes, but to lessen the quality of the ovarian response to the hCG injection. Basal FSH levels may be of value in predicting ART success in women with the disease. Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Fertil Steril. 2010 May 28. [Epub ahead of print]

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 muM had no effect on ESC attachment. Treatment with 0.5 muM, 2 muM, and 10 muM of imatinib reduced ESC proliferation by 30%, 72%, and 76%, respectively. The 0.1 muM dose of imatinib had no effect on proliferation. Treatment with 5 muM and 10 muM of imatinib reduced ESC invasion by 30% and 73%, respectively. The 2 muM 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.

Gynecol Endocrinol. 2010 Jun 17. [Epub ahead of print]

Endometrial aromatase mRNA as a possible screening tool for advanced endometriosis and adenomyosis.

Hatok J, Zubor P, Galo S, Kirschnerova R, Dobrota D, Danko J, Racay P.

Department of Medical Biochemistry, Jessenius Faculty of Medicine, Comenius University in Bratislava, Mala Hora 4, 036 01 Martin, Slovak Republic.

Endometriosis (ENDs) and adenomyosis (ADNs) are estrogen-dependent diseases. The aim of this study was to determine the clinical usefulness of examining endometrial biopsy specimens for aromatase cytochrome P450 (CYP19) as a diagnostic importance for endometriosis and adenomyosis. In general, the RT-PCR analyses of 101 samples revealed increased aromatase mRNA expression in eutopic endometrium in women with endometriosis and adenomyosis compared to healthy controls (p = 0.0002). The highest number of positive cases (93.3%) of CYP19 mRNA expression was detected in women with advanced disease stages. Concrete expression of CYP19 mRNA level in controls was 0.68 compared to patients with ADNs (1.21), ENDsL stage I-II (1.15) and ENDsA stage III-IV (1.65) (p < 0.0001), respectively. The possible influence of increased body mass index on aromatase expression in each group showed in controls an insignificant slight increase of aromatase expression, contrary to cases where this trend was the opposite. The results point to the higher (2.45-fold) difference in aromatase expression in patients with endometriosis stage III-IV compared to controls and provide direct evidence that screening for eutopic endometrial aromatase expression in combination with clinical data could be of discriminative value in the prediction of estrogen-dependent diseases, independent from body mass index.

MMW Fortschr Med. 2010 May 20;152(20):21.

Young woman with recurrent cramping abdominal pain. What is in back of the submucous space occupying lesion of the sigmoid colon?

[Article in German]

Stiefelhagen P.

Histol Histopathol. 2010 Aug;25(8):1009-16.

Immunohistochemical analysis of steroid receptors in ovaries of postmenopausal women–effects of aging and hormone status.

Brodowska A, Laszczyńska M, Starczewski A, Brodowski J, Masiuk M, Domagala W.

Department of Reproduction and Gynecology, Pomeranian Medical University, Szczecin, Poland.

Current knowledge on immunolocalization and immunoexpression of steroid hormone receptors, especially estrogen receptor alpha (ER-alpha), progesterone receptor (PR) and androgen receptor (AR) in normal ovaries in postmenopausal women is not complete. The recognition of localization of these receptors in postmenopausal women is crucial, as many of these women receive estro-progestagene therapy, and its participation in the pathogenesis of ovarian cancer should be carefully studied. In our paper we present the results of immunohistochemical studies performed on samples from 100 post-menopausal women (aged: 48 to 60 years) who did not use hormonal therapy. The ovaries were removed during elective operation due to uterine leiomyoma, endometriosis and/or prolapsed uterine. PR, ER-alpha and AR were detected in the normal ovaries of postmenopausal women in stroma and in ovarian surface epithelium, as well as in its invagination and in epithelial inclusion cysts. The expression of PR and AR did not change, while the expression of ER-alpha decreased in time from menopause, and it was also detected in patients more than 10 years after menopause. Women older than 60 were not included in the study. The concentration of selected hormones was measured in the serum. The immunohistochemical expression of PR and AR were similar in all examined patients and did not correlate with FSH, LH, T, A, DHEAS concentrations in serum, while immunohistochemical expression of ER-alpha correlated with FSH, LH, T, A, DHEAS concentrations in serum. The significant correlation of decreasing expression of ER-alpha in normal ovarian tissue and decreasing concentrations of T, A and DHEAS in serum were found, as well as increasing serum concentrations of FSH and LH.

Hum Reprod Update. 2010 Jun 14. [Epub ahead of print]

Physiological pathways and molecular mechanisms regulating uterine contractility.

Aguilar HN, Mitchell BF.

Department of Physiology, University of Alberta, Edmonton, Alberta, Canada.

BACKGROUND Uterine contractile activity plays an important role in many and varied reproductive functions including sperm and embryo transport, implantation, menstruation, gestation and parturition. Abnormal contractility might underlie common and important disorders such as infertility, implantation failure, dysmenorrhea, endometriosis, spontaneous miscarriage or preterm birth. METHODS A systematic review of the US National Library of Medicine was performed linking ‘uterus’ or ‘uterine myocyte’ with ‘calcium ion’ (Ca(2+)), ‘myosin light chain kinase’ and ‘myosin light chain phosphatase’. This led to many cross-references involving non-uterine myocytes and, where relevant, these data have been incorporated into the following synthesis. RESULTS We have grouped the data according to three main components that determine uterine contractility: the contractile apparatus; electrophysiology of the myocyte including excitation-contraction coupling; and regulation of the sensitivity of the contractile apparatus to Ca(2+). We also have included information regarding potential therapeutic methods for regulating uterine contractility. CONCLUSIONS More research is necessary to understand the mechanisms that generate the frequency, amplitude, duration and direction of propagation of uterine contractile activity. On the basis of current knowledge of the molecular control of uterine myocyte function, there are opportunities for systematic testing of the efficacy of a variety of available potential pharmacological agents and for the development of new agents. Taking advantage of these opportunities could result in an overall improvement in reproductive health.

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