J Clin Endocrinol Metab. 2010 Nov;95(11):E300-9. Epub 2010 Aug 11.

Altered retinoid uptake and action contributes to cell survival in endometriosis.

Pavone ME, Reierstad S, Sun H, Milad M, Bulun SE, Cheng YH.

Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, Illinois 60611, USA.

CONTEXT: Retinoic acid (RA) controls multiple biological processes via exerting opposing effects on cell survival. Retinol uptake into cells is controlled by stimulated by RA 6 (STRA6). RA is then produced from retinol in the cytosol. Partitioning of RA between the nuclear receptors RA receptor α and peroxisome-proliferator-activated receptor β/δ is regulated by cytosol-to-nuclear shuttling proteins cellular RA binding protein 2 (CRABP2) and fatty acid binding protein 5 (FABP5), which induce apoptosis or enhance survival, respectively. The roles of these mechanisms in endometrium or endometriosis remain unknown.

OBJECTIVE: The aim was to determine the regulation of retinoid uptake and RA action in primary stromal cells from endometrium (n = 10) or endometriosis (n = 10).

RESULTS: Progesterone receptor was necessary for high STRA6 and CRABP2 expression in endometrial stromal cells. STRA6, which was responsible for labeled retinoid uptake, was strikingly lower in endometriotic cells compared to endometrial cells. CRABP2 knockdown in endometrial cells increased survival, and FABP5 knockdown in endometriotic cells decreased survival without altering the expression of downstream nuclear retinoic acid receptor α and peroxisome-proliferator-activated receptor β/δ.

CONCLUSIONS: In endometrial stromal cells, progesterone receptor up-regulates expression of STRA6 and CRABP2, which control retinol uptake and growth-suppressor actions of RA. In endometriotic stromal cells, decreased expression of these genes leads to decreased retinol uptake and dominant FABP5-mediated prosurvival activity.

J Minim Invasive Gynecol. 2010 Nov-Dec;17(6):749-53.

Fourteen-year experience with laparoscopic ventrosuspension in patients with retroverted and retroflected uterus and pelvic pain syndromes.

Ott J, Nouri K, Demmel M, Zafraani S, Greilberger U, Huber JC, Mayerhofer K.

Department of Gynaecologic Endocrinology and Reproductive Medicine, Medical University of Vienna, Vienna, Austria.

BACKGROUND: In women with a retroverted uterus, who have dyspareunia, chronic pelvic pain, or dysmenorrhea, laparoscopic ventrosuspension of the uterus has been reported effective in achieving symptom relief.

STUDY OBJECTIVE: To critically review our experience with our method of laparoscopic ventrosuspension.

DESIGN: Cohort study (Canadian Task Force classification II-3).

SETTING: Tertiary care center.

PATIENTS: Sixty-three women who had undergone laparoscopic ventrosuspension for treatment of pain syndromes during 1995 through 2008.

INTERVENTIONS: Laparoscopic ventrosuspension, and a questionnaire about the long-term outcome of the operation.

MEASUREMENTS AND MAIN RESULTS: There were no adverse events except for 2 repeat operations within 3 postoperative days. Forty-nine women (77.8%) answered the questionnaire about long-term outcome, and in these patients, significant pain relief was achieved (p <.001). Pain levels decreased, based on a numeric rating scale, from a mean (SD) of 6.35 (1.92) to 0.97 (1.40) in patients without endometriosis, and from 6.93 (2.09) to 3.80 (2.08) in those with endometriosis. Of 34 patients without endometriosis, 1 (2.9%) stated that the operation had not led to symptom relief, compared with 4 of 15 (26.7%) with endometriosis (p = .03).

CONCLUSION: Laparoscopic ventrosuspension is clearly beneficial in women with a retroverted and retroflected uterus who have pelvic pain syndromes, even in the long term.

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

J Mol Endocrinol. 2010 Nov;45(5):291-9. Epub 2010 Aug 23.

The high level of RANTES in the ectopic milieu recruits macrophages and induces their tolerance in progression of endometriosis.

Wang XQ, Yu J, Luo XZ, Shi YL, Wang Y, Wang L, Li DJ.

Laboratory for Reproductive Immunology, Hospital and Institute of Obstetrics and Gynecology, IBS, Fudan University Shanghai Medical College, Shanghai 200011, People’s Republic of China.

RANTES (C-C chemokine, regulated on activation, normal T cell expressed and secreted) is involved in progression of endometriosis, but the precise mechanism is understood inadequately. This study is to elucidate the roles of RANTES in macrophage recruitment and tolerance in the endometriotic milieu. The expression of RANTES was analyzed by immunohistochemistry. The cell co-cultures were applied to simulate the endometriotic milieu to investigate the regulation of RANTES secretion and its receptor CCR1 expression. Transwell migration assay was used for chemotaxis of U937 cells (macrophage line) to endometrial stromal cells (ESCs) and/or human pelvic mesothelial cells. The expression of CCR1 was analyzed by RT-PCR and qPCR in transcription and by western blot in translation respectively. Concentrations of RANTES, IL10, and IL12p70 were determined by ELISA. The phenotype of U937 cells and apoptosis of ESCs were analyzed by flow cytometry. We have found that the expression of RANTES is significantly higher in the endometriotic tissue and eutopic endometrium than that of the normal endometrium without endometriosis. The combination of 17β-estradiol and dioxin 2,3,7,8-tetrachlorodibenzo-p-dioxin increases significantly RANTES secretion in the endometriosis-associated cell co-culture which can recruit more macrophages, upregulate CCR1 expression, and induce tolerant phenotype, which inhibits the apoptosis of ESC in the milieu. In conclusion, the higher levels of RANTES in the ectopic milieu facilitate the onset and progression of endometriosis by macrophage recruitment and tolerance that in turn inhibits apoptosis and enhances growth of ESC.

J Pathol. 2010 Nov;222(3):261-70.

Oestrogen-induced epithelial-mesenchymal transition of endometrial epithelial cells contributes to the development of adenomyosis.

Chen YJ, Li HY, Huang CH, Twu NF, Yen MS, Wang PH, Chou TY, Liu YN, Chao KC, Yang MH.

Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan.

Adenomyosis is an oestrogen-dependent disease caused by a downward extension of the endometrium into the uterine myometrium. Epithelial-mesenchymal transition (EMT) endows cells with migratory and invasive properties and can be induced by oestrogen. We hypothesized that oestrogen-induced EMT is critical in the pathogenesis of adenomyosis. We first investigated whether EMT occurred in adenomyotic lesions and whether it correlated with serum 17β-oestradiol (E2) levels. Immunohistochemistry was performed on adenomyotic lesions and corresponding eutopic endometrium samples from women with adenomyosis. Endometria from women without endometrial disorders were used as a control. In the epithelial component of adenomyotic lesions, vimentin expression was up-regulated and E-cadherin expression was down-regulated compared to the eutopic endometrium, suggesting that EMT occurs in adenomyosis. In adenomyosis, the serum E2 level was negatively correlated with E-cadherin expression in the epithelial components of the eutopic endometrium and adenomyotic lesions, suggesting the involvement of oestrogen-induced EMT in endometrial cells. In oestrogen receptor-positive Ishikawa endometrial epithelial cells, oestrogen induced a morphological change to a fibroblast-like phenotype, a shift from epithelial marker expression to mesenchymal marker expression, increased migration and invasion, and up-regulation of the EMT regulator Slug. Raloxifene, a selective oestrogen receptor modulator, abrogated these effects. To determine the role of oestrogen-induced EMT in the implantation of ectopic endometrium, we xenotransplanted eutopic endometrium or adenomyotic lesions from adenomyosis patients into ovariectomized SCID mice. The implantation of endometrium was oestrogen-dependent and was suppressed by raloxifene. Collectively, these data highlight the crucial role of oestrogen-induced EMT in the development of adenomyosis and suggest that raloxifene may be a potential therapeutic agent for adenomyosis patients.

Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

J Reprod Immunol. 2010 Nov;86(2):141-7. Epub 2010 Jul 1.

Endometriosis research: animal models for the study of a complex disease.

Tirado-González I, Barrientos G, Tariverdian N, Arck PC, García MG, Klapp BF, Blois SM.

Charité, Department of Internal Medicine and Dermatology, Medicine University of Berlin, Berlin, Germany.

Endometriosis is a common gynaecological disease that is characterized and defined as the presence of endometrial tissue outside the uterus, causing painful periods and subfertility in approximately 10% of women. After more than 50 years of research, little is known about the mechanisms underlying the development and establishment of this condition. Animal models allow us to study the temporal sequence of events involved in disease establishment and progression. Also, because this disease occurs spontaneously only in humans and non-human primates and there are practical problems associated with studying the disease, animal models have been developed for the evaluation of endometriosis. This review describes the animal models for endometriosis that have been used to date, highlighting their importance for the investigation of disease mechanisms that would otherwise be more difficult to elucidate, and proposing new alternatives aimed at overcoming some of these limitations.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

J Sex Res. 2010 Nov;47(6):513-27.

Sexual functioning following elective hysterectomy: the role of surgical and psychosocial variables.

Peterson ZD, Rothenberg JM, Bilbrey S, Heiman JR.

Department of Psychology and Institute for Women and Gender Studies, University of Missouri-St. Louis, USA. petersonz@umsl.edu

In this article, two studies were conducted to investigate the surgical and psychosocial correlates of women’s post-hysterectomy sexual functioning. In Study 1, sexual functioning was measured in an online convenience sample of 65 women who had undergone elective hysterectomy. Results suggested that most women experienced improved sexual functioning after their hysterectomy. Women who underwent hysterectomy to treat endometriosis reported less improvement in sexual functioning as compared to women who had hysterectomies for other indications, and women who had abdominal hysterectomies reported less improvement in sexual functioning as compared to women who had vaginal hysterectomies. Sexual functioning post-hysterectomy was associated with psychosocial variables, particularly body esteem and relationship quality. In Study 2, sexual functioning was investigated at two time points three to five months apart in a sample of 14 women who reported developing sexual problems following their elective hysterectomies. Results suggested that, among women suffering from post-hysterectomy sexual dysfunction, sexual pain and difficulty with orgasm increased over time.

J Surg Res. 2010 Nov;164(1):e77-81. Epub 2010 Aug 15.

Abdominal wall endometrioma; a 10-year experience and brief review of the literature.

Bektaş H, Bilsel Y, Sari YS, Ersöz F, Koç O, Deniz M, Boran B, Huq GE.

General Surgery Department, Istanbul Training and Research Hospital, Istanbul, Turkey. hasanbektas3417@hotmail.com

BACKGROUND: Abdominal wall endometrioma is a rare condition, which usually develops in a surgical scar of Cesarean section or hysterectomy. Certain factors relating to knowledge of the clinical pattern of this disease make correct diagnosis and treatment difficult. The aim was to identify the different forms of presentation of this disease entity through publishing the results from our experience of surgical management of such lesions.

METHODS: Patients diagnosed with abdominal wall endometrioma over a period of 10 y were identified from the comprehensive surgical database of our institution. The age, parity, symptoms, previous surgeries, initial diagnosis, diagnostic modalities, current operation, and recurrences were surveyed and analyzed.

RESULTS: There were 40 patients with a mean age of 32.3 ± 5.2 y. All of the patients (100%, n = 40) had an abdominal mass in or adjacent to surgical scars. The main symptom was pain, noncyclic (45%, n =18), or cyclic (40%, n = 16) in nature. The mean duration of symptoms was 18.2 ± 23.4 mo. The preoperative diagnosis was correct in 47.5% (n = 19) of the cases. Surgical treatment failed in 3 cases (3/33, 9.1%), and the operations were performed once again.

CONCLUSIONS: Abdominal wall endometriosis may be difficult to diagnose as it is comparatively an unfamiliar entity that has not received its due attention among general surgeons, so far. Therefore, in patients with a palpable subcutaneous mass in or around surgical scars with a history of violation of uterus, a thorough history and physical examination is necessary, and usually sufficient to make correct diagnosis of endometrioma.

Copyright © 2010 Elsevier Inc. All rights reserved.

J Thorac Cardiovasc Surg. 2010 Nov;140(5):1189-90.

Pericardial, pleural, and diaphragmatic endometriosis.

Ceccaroni M, Clarizia R, Placci A.

Gynecologic Oncology Division, International School of Surgical Anatomy, Sacred Heart Hospital, Negrar, Verona, Italy. roberto.clarizia@gmail.com

J Womens Health (Larchmt). 2010 Nov;19(11):2063-9. Epub 2010 Sep 11.

Does controlled ovarian hyperstimulation in women with a history of endometriosis influence recurrence rate?

Coccia ME, Rizzello F, Gianfranco S.

Department of Gynaecology, Perinatology and Human Reproduction, University of Florence, Florence, Italy. cocciame@tin.it

BACKGROUND: Endometriosis is a common estrogen-dependent disease. The aim of this study was to assess whether controlled ovarian hyperstimulation (COH) for assisted reproductive technology (ART) was associated with an increased incidence in endometriosis recurrence as documented by transvaginal ultrasound (TV-US).

METHODS: In a retrospective cohort study of 592 patients submitted to laparoscopy for endometriosis, 177 with infertility-related endometriosis who underwent a periodic ultrasound follow-up after laparoscopy were selected. Women who started ART after laparoscopy (n = 90) were compared with the control group, who did not undergo ART (n = 87). Recurrence of endometriosis was defined as the presence of endometriotic lesions observed through TV-US.

RESULTS: During a long-term TV-US follow-up (1-15 years), 40 (22.6%) recurrences were observed. Patients submitted to ART showed a cumulative recurrence rate similar to that of the control group (28.6% and 37.9% respectively, p = 0.471). Recurrent lesions were ovarian cysts (47.5%), ovarian nodules (37.5%), and rectovaginal disease (15%). The stratified analysis based on stages of endometriosis and pelvic pain did not show differences.

CONCLUSIONS: Gonadotropin treatments do not seem to affect the natural history of endometriotic lesions. The most important prognostic factors in recurrent disease observed by TV-US seem to be the stage of endometriosis and the presence of pelvic pain at the time of the first laparoscopic treatment.

Mol Hum Reprod. 2010 Nov;16(11):818-34. Epub 2010 Jul 13.

Adult stem cells in the endometrium.

Gargett CE, Masuda H.

Department of Obstetrics and Gynaecology and The Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, VIC, 3168, Australia. caroline.gargett@monash.edu

Rare cells with adult stem cell activity were recently discovered in human endometrium. Endometrial stem/progenitor cell candidates include epithelial, mesenchymal and endothelial cells, and all may contribute to the rapid endometrial regeneration following menstruation, rather than a single candidate. Endometrial mesenchymal stem-like cells (eMSC) are prospectively isolated as CD146(+)PDGF-Rβ(+) cells and are found in both basalis and functionalis as perivascular cells. Epithelial progenitor cells are detected in colony forming unit assays but their identity awaits elucidation. They are postulated to reside in the basalis in gland bases. Endometrial stem/progenitor cells may be derived from endogenous stem cells, but emerging evidence suggests a bone marrow contribution. Endometrial endothelial progenitor cells are detected as side population cells, which express several endothelial cell markers and differentiate into endometrial glandular epithelial, stromal and endothelial cells. Investigating endometrial stem cell biology is crucial to understanding normal endometrial physiology and to determine their roles in endometrial proliferative diseases. The nature of endometriosis suggests that initiation of ectopic endometrial lesions involves endometrial stem/progenitor cells, a notion compatible with Sampson’s retrograde menstruation theory and supported by the demonstration of eMSC in menstrual blood. Evidence of cancer stem cells (CSC) in endometrial cancer indicates that new avenues for developing therapeutic options targeting CSC may become available. We provide an overview of the accumulating evidence for endometrial stem/progenitor cells and their possible roles in endometrial proliferative disorders, and discuss the unresolved issues.

Pain. 2010 Nov;151(2):307-22. Epub 2010 Jul 16.

Viscero-visceral hyperalgesia: characterization in different clinical models.

Giamberardino MA, Costantini R, Affaitati G, Fabrizio A, Lapenna D, Tafuri E, Mezzetti A.

Department of Medicine and Science of Aging, G. D’Annunzio University of Chieti, Italy. mag@unich.it

Comment in:

Co-existing algogenic conditions in two internal organs in the same patient may mutually enhance pain symptoms (viscero-visceral hyperalgesia). The present study assessed this phenomenon in different models of visceral interaction. In a prospective evaluation, patients with: (a) coronary artery disease (CAD)+gallstone (Gs) (common sensory projection: T5); (b) irritable bowel syndrome (IBS)+dysmenorrhea (Dys) (T10-L1); (c) dysmenorrhea/endometriosis+urinary calculosis (Cal)(T10-L1); and (d) gallstone+left urinary calculosis (Gs+LCal) (unknown common projection) were compared with patients with CAD, Gs, IBS, Dys or Cal only, for spontaneous symptoms (number/intensity of pain episodes) over comparable time periods and for referred symptoms (muscle hyperalgesia; pressure/electrical pain thresholds) from each visceral location. In patients’ subgroups, symptoms were also re-assessed after treatment of each condition or after no treatment. (a) CAD+Gs presented more numerous/intense angina/biliary episodes and more referred muscle chest/abdominal hyperalgesia than CAD or Gs; cardiac revascularization or cholecystectomy also reduced biliary or cardiac symptoms, respectively (0.001<p<0.05). (b) IBS+Dys had more intestinal/menstrual pain and abdomino/pelvic muscle hyperalgesia than IBS or Dys; hormonal dysmenorrhea treatment also reduced IBS symptoms; IBS dietary treatment also improved dysmenorrhea (0.001<p<0.05) while no treatment of either conditions resulted in no improvement in time of symptoms from both. (c) Cal+Dys had more urinary/menstrual pain and referred lumbar/abdominal hyperalgesia than Cal or Dys; hormonal dysmenorrhea treatment/laser treatment for endometriosis also improved urinary symptoms; lithotripsy for urinary stone also reduced menstrual symptoms (0.001<p<0.05). (d) In Gs+LCal, cholecystectomy or urinary lithotripsy did not improve urinary or biliary symptoms, respectively. Mechanisms of viscero-visceral hyperalgesia between organs with documented partially common sensory projection probably involve sensitization of viscero-viscero-somatic convergent neurons.

Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Prog Urol. 2010 Nov;20(12):1089-94. Epub 2010 Sep 28.

Therapeutic education and alternative medicine

[Article in French]

Sibert L, Rigaud J, Delavierre D, Labat JJ.

Service d’urologie, EA 4308, hôpital Charles-Nicolle, CHU de Rouen, université de Rouen, 1, rue de Germont, 76000 Rouen, France. louis.sibert@chu-rouen.fr

OBJECTIVE: To review the most common Complementary and Alternative Medical (CAM) therapies described for chronic pelvic pain care and to analyze their results as reported in the literature.

MATERIAL AND METHODS: Review of articles and consensus conferences published on this subject in the Medline (PubMed) database, selected according to their scientific relevance.

RESULTS: Lifestyle interventions have a positive impact on patients’ self-management of their chronic pain. Positive outcomes are associated with well-balanced diet, dietary changes and certain dietary supplementations for bladder pain syndrome and chronic pelvic pain syndrome. Limited data exist supporting the use of acupuncture for chronic pelvic pain, endometriosis, bladder pain syndrome and urethral pain syndrome. There is no evidence for homeopathy and mesotherapy.

CONCLUSIONS: Published data on many CAM therapies suggest their potential as complementary treatment options of chronic pelvic pain. As conventional treatments, CAM therapies warrant further studies to assist in their validation as permanent treatment options for this patient population.

Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Prog Urol. 2010 Nov;20(12):1027-34. Epub 2010 Oct 16.

Global approach to chronic pelvic and perineal pain: from the concept of organ pain to that of dysfunction of visceral pain regulation systems

[Article in French]

Labat JJ, Riant T, Delavierre D, Sibert L, Watier A, Rigaud J.

Centre fédératif de pelvipérinéologie, clinique urologique, CHU de Nantes, 44093 Nantes, France. jjlabat@chu-nantes.fr

OBJECTIVE: Analysis of complex pelvic and perineal pain.

MATERIAL AND METHODS: Review of the literature concerning the various types of functional pelvic pain.

RESULTS: Various forms of pelvic pain are frequently associated: painful bladder syndrome (interstitial cystitis), irritable bowel syndrome, endometriosis pain, vulvodynia, chronic pelvic pain syndrome (chronic prostatitis). Pelvic pain is often associated with fibromyalgia or complex regional pain syndrome (reflex sympathetic dystrophy). The pathophysiological mechanisms involved in these syndromes are all very similar, suggesting a triggering element, neurogenic inflammation, reflex muscular and autonomic responses, central hypersensitization, emotional reactions and biopsychosocial consequences.

DISCUSSION: The concept of visceral pain is evolving and, in practice, complex pelvic pain can comprise neuropathic components, complex regional pain syndrome components, hypersensitization components, and emotional components closely resembling posttraumatic stress syndrome.

CONCLUSIONS: When pain cannot be explained by an organ disease, the pain must be considered to be expressed via this organ. Chronic pelvic and perineal pain can become self-perpetuating and identification of its various mechanisms can allow the proposal of individually tailored treatments.

Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Prog Urol. 2010 Nov;20(12):1010-8.

Endometriosis and chronic pelvic pain

[Article in French]

Roman H, Bourdel N, Rigaud J, Delavierre D, Labat JJ, Sibert L.

Clinique gynécologique et obstétricale, CHU de Rouen, 76000 Rouen, France.

OBJECTIVES: To analyse pathophysiology and clinical symptoms of chronic pelvic pain and their therapeutic care.

MATERIAL AND METHODS: Review of articles and consensus conferences published on this subject in the Medline(®) (PubMed(®)) database.

RESULTS: Pain importance and endometriosis lesion size are somewhat linked. In the case of chronic pains, endometriosis lesions are not always the only cause of the pain. Imaging consists mostly of MRI and transvaginal ultrasonography. Treatment must be offered to patients with painful endometriosis. Hormonal treatment meant to cause amenorrhea is recommended to improve dysmenorrhea, dyspareunia and chronic pains. Endometriosis should be confirmed by pathological or surgical findings, before prolonged treatment is undergone. Prolonged postoperative amenorrhea significantly decreases pain and lesion relapse. Surgical treatment is effective on painful symptoms and is recommended in the event of painful endometriosis. Undergoing surgery is recommended only if individual benefit exceeds risk.

CONCLUSIONS: Surgical treatment should aim at improving symptoms rather than systematically removing every endometriosis lesion. Diagnosis of endometriosis lesion at an early stage is currently a major part of public health policy.

Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Prog Urol. 2010 Nov;20(12):967-72. Epub 2010 Sep 29.

Pelvic sexual pain

[Article in French]

Sibert L, Safsaf A, Rigaud J, Delavierre D, Labat JJ.

Service d’urologie, EA 4308, hôpital Charles-Nicolle, CHU de Rouen, université de Rouen, 1, rue de Germont, 76000 Rouen, France. louis.sibert@chu-rouen.fr

OBJECTIVE: To colligate the clinical and ethiopathogenical elements to take into account in the assessment of sexual activity-related chronic pelvic and perineal pain, in the male as well as in the female subject.

SUBJECTS AND METHODS: Review of articles and consensus conferences published on this subject in the Medline (Pubmed) database, selected according to their scientific relevance.

RESULTS: In the female subject, only dyspareunia has benefitted from a consensual definition. Deep dyspareunia must start investigations in search of pelvic organs disorders, endometriosis, painful bladder syndrome adhesions. Superficial dyspareunia can be a part of provoked vestibulodynia. Vaginismus can be linked to a local disorder, but can also be caused by an excess of nociception. In the male subject, painful ejaculation must start investigation in search of a local urological disorder. It can also be of iatrogenous origin, or be included in a chronic pelvic pain syndrome. Although less documented, other pelvic and perineal pain syndrome, coitus-related or not, exist in the male subject.

CONCLUSION: Assessment of these sexual dysfunctions is primarily based on history taking and clinical examination. In the absence of systematically researched organic disorder, these pains can be part of functional disorders, in which case a global assessment must be undergone, by taking into account all aspects of the pain, including emotional aspects.

Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Prog Urol. 2010 Nov;20(12):872-85. Epub 2010 Sep 29.

Chronic pelvic pain: epidemiology and economic impact

[Article in French]

Sibert L, Rigaud J, Delavierre D, Labat JJ.

Service d’urologie, EA 4308, hôpital Charles-Nicolle, CHU de Rouen, université de Rouen, 1, rue de Germont, 76000 Rouen, France. louis.sibert@chu-rouen.fr

OBJECTIVE: To combine epidemiological and health economics data concerning urological chronic pelvic pain syndromes.

MATERIAL: Review of articles concerning this topic in the Medline (PubMed) database, chosen according to their scientific relevance.

RESULTS: Prevalences are about 10,000/100,000 for chronic pelvic pain syndrome/chronic prostatis, 239 to 306/100,000 for bladder pain syndrome/interstitial cystitis, 15,000 to 20,000/100,000 for post-vasectomy testis and epididymis pain, 14,000/100,000 concerning deep female dyspareunia, 1000 to 9000/100,000 for male ejaculation or orgasma-related pain, 15,000 to 21,000/100,000 for female chronic pelvic pain, of which one third is related to endometriosis. Little has been published about the frequency of other chronic pelvic and perineal pain syndromes. The financial impact is comparable to other more frequent chronic diseases, with costs definitely above what the prevalences would have led to believe.

CONCLUSION: The frequency of pelvic disease association, their predisposing factors, common environments and comordities suggest a possible common origin. This epidemiological data highlights the benefit of a multidisciplinary approach of chronic pelvic and perineal pain. This could lead to a better understanding of involved mechanisms, and ultimately treatment options.

Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Reprod Sci. 2010 Nov;17(11):1016-23.

Deregulation of LOXL1 and HTRA1 gene expression in endometriosis.

Blassioli Dentillo D, Meola J, Rosa E Silva JC, Giuliatti S, Araujo Silva W Jr, Ferriani RA, Martelli L.

Department of Genetics, School of Medicine of Ribeirao Preto, University of Sao Paulo, Avenida Bandeirantes, Ribeirao Preto, Sao Paulo, Brazil. danieldentillo@yahoo.com.br

Endometriosis is a gynecologic disease characterized by the presence of endometrial tissue outside the uterine cavity. Although 15% of the female population in reproductive age is affected by endometriosis, its pathogenesis remains unclear. According to the most accepted pathogenesis hypothesis, endometrial fragments from the menstrual phase are transported through the uterine tubes to the peritoneal cavity, where they undergo implantation and growth, invading adjacent tissues. However, the establishment of the disease requires that endometrial cells present molecular characteristics favoring the onset and progression of ectopic implantation. In this investigation, we analyzed the differential gene expression profiles of peritoneal and ovarian endometriotic lesions compared to the endometrial tissue of nonaffected women using rapid subtraction hybridization (RaSH). In our study, this method was applied to samples of endometriotic lesions from affected women and to biopsies of endometrium of healthy women without endometriosis, where we could identify 126 deregulated genes. To evaluate the expression of genes found by RaSH method, we measured LOXL1, HTRA1, and SPARC genes by real-time polymerase chain reaction. Significant different expression was obtained for HTRA1 and LOXL1, upregulated in the ectopic endometrium, suggesting that these genes are involved in the physiopathology of endometriosis and may favor the viability of endometrial cells at ectopic sites.

Reprod Sci. 2010 Nov;17(11):987-94. Epub 2010 Aug 18.

Estrogen induces distinct patterns of microRNA expression within the mouse uterus.

Nothnick WB, Healy C.

Department of Obstetrics and Gynecology, University of Kansas Medical Center, Kansas City, KS, USA. wnothnic@kumc.edu

Control of estrogenic activity within the uterus is evident as unopposed estrogen action is associated with endometrial pathologies such as endometriosis and endometrial carcinoma. MicroRNAs (miRNAs) have emerged as important posttranscriptional regulators, which are postulated to fine-tune the actions of steroids in many systems including the uterus. The objective of the current study was to examine uterine expression of miRNAs in response to estrogen treatment within the mouse uterus using an ovariectomized, steroid-reconstituted mouse model. MicroRNA microarray analysis and subsequent quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) verification revealed that expression of mirn155, mirn429, and mirn451 was significantly increased by estrogen administration whereas mirn181b and mirn204 expression was significantly reduced. Pretreatment with the estrogen receptor (ER) antagonist ICI 182,780 confirmed that estrogen regulation was mediated via the classical ER pathway. This study demonstrates that estrogen regulates specific miRNAs within the murine uterus, which may participate in posttranscriptional regulation of estrogen-regulated genes.

Reprod Sci. 2010 Nov;17(11):995-1005. Epub 2010 Aug 9.

Promoter hypermethylation of progesterone receptor isoform B (PR-B) in adenomyosis and its rectification by a histone deacetylase inhibitor and a demethylation agent.

Jichan Nie, Xishi Liu, Guo SW.

Shanghai OB/GYN Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Adenomyosis is a fairly common gynecologic disease with unknown pathogenesis. We sought to investigate as to whether the promoter of progesterone receptor isoform B (PR-B) is hypermethylated in adenomyosis and to investigate the treatment of ectopic endometrial stromal cells with trichostatin A (TSA), a histone deacetylase inhibitor (HDI), and 5-aza-2-deoxycytidine (ADC), a demethylation agent, on PR-B gene and protein expression, and on cell viability. Ectopic endometrial tissue specimens were obtained from 9 women with adenomyosis whereas control endometrial tissue samples were obtained from 8 women with surgically diagnosed benign ovarian cysts but without any clinical history of endometriosis/adenomyosis/ myoma. Endometrial stromal cells were isolated, purified, cultured, and analyzed by methylation-specific polymerase chain reaction (PCR), real-time reverse transcriptase PCR (RT-PCR), and Western blot analysis, cell viability assays, and fluorescence-activated cell sorting. We found that none of the normal endometrial stromal cells had PR-B promoter methylation. In contrast, 2 out of 3 ectopic endometrial stromall cells had PR-B hypermethylation (P < .05). The treatment with both TSA and ADC elevated PR-B gene and protein expression in ectopic, but not in normal, endometrial stromal cells. Both TSA and ADC treatment dose-dependently reduced cell viability of ectopic endometrial stromal cells. Trichostatin A and ADC treatment also suppressed the cell cycle progression in ectopic endometrial stromal cells. Thus, this study provides the first piece of evidence that adenomyosis has epigenetic aberration and may also be an epigenetic disease amenable to rectification by pharmacological means. This perspective may shed new light onto the pathogenesis of adenomyosis and lead to novel ways to treat the disease.

Reprod Toxicol. 2010 Nov;30(3):365-9. Epub 2010 May 16.

Organochlorine pesticides and endometriosis.

Cooney MA, Buck Louis GM, Hediger ML, Vexler A, Kostyniak PJ.

Epidemiology Branch, Division of Epidemiology, Statistics and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health & Human Development, 6100 Executive Blvd, Rockville, MD 20852, USA. cooneyma@mail.nih.gov

Limited study of persistent organochlorine pesticides (OCPs) and endometriosis has been conducted. One hundred women aged 18-40 years who were undergoing laparoscopy provided 20 cm(3) of blood for toxicologic analysis and surgeons completed operative reports regarding the presence of endometriosis. Gas chromatography with electron capture was used to quantify (ng/g serum) six OCPs. Logistic regression was utilized to estimate the adjusted odds ratios (aOR) and 95% confidence intervals (CI) for individual pesticides and groups based on chemical structure adjusting for current cigarette smoking and lipids. The highest tertile of aromatic fungicide was associated with a fivefold risk of endometriosis (aOR=5.3; 95% CI, 1.2-23.6) compared to the lowest tertile. Similar results were found for t-nonachlor and HCB. These are the first such findings in a laproscopic cohort that suggest an association between OCP exposure and endometriosis. More prospective studies are necessary to ensure temporal ordering and confirm these findings.

Copyright © 2010 Elsevier Inc. All rights reserved.

Tech Coloproctol. 2010 Nov;14 Suppl 1:S25-7.

Perineal endometriosis: a case report and review of the literature.

Odobasic A, Pasic A, Iljazovic-Latifagic E, Arnautalic L, Odobasic A, Idrizovic E, Dervisefendic M, Dedić L.

Surgery Clinic, University Clinical Center Tuzla, Trnovac bb, 75000,Tuzla, Bosnia and Herzegovina. amer.o@bih.net.ba

Endometriosis is the presence of endometrial-like tissue outside the uterine cavity, which most commonly affects peritoneal surfaces, ovaries and uterine ligaments. Even it is quite rare, endometriosis may affect the vulva, vagina, rectovaginal septum or perineal region, generally secondary to obstetric or surgical trauma. In this case report, we present a patient with perineal endometriosis in an episiotomy scar. Diagnostic tools used included transvaginal and endorectal ultrasonography (USG), magnetic resonance imaging (MRI) and biopsy. The endometriotic mass was wide-excised together with episiotomy scar. The recovery was uneventful with excellent functional and esthetic results. Six months after operation, woman is asymptomatic. According to the literature and our own experience, wide excision of endometriotic tissue seems to be the best chance of cure with satisfactory functional results and should be recommended.

Tech Coloproctol. 2010 Nov;14 Suppl 1:S87-9.

Large bowel obstruction due to endometriosis.

Pramateftakis MG, Psomas S, Kanellos D, Vrakas G, Roidos G, Makrantonakis A, Kanellos I.

Surgical Department of European Medical Center, Antheon 1, Panorama, 55236 Thessaloniki, Greece. mpramateftakis@hotmail.com

We report on three cases of premenopausal female patients with large bowel endometriosis causing intermittent obstruction.

Tunis Med. 2010 Nov;88(11):841-3.

A case of cutaneous endometriosis developed on an abdominal scar.

Attia L, Ben Temime R, Sidhom J, Sahli A, Makhlouf T, Chachia A, Koubaa A, Zermani R.

Background: Endometriosis is characterized by the presence of an ectopic endometrial tissue. It affects between 1% and 5% of women in reproductive age. Its main clinical symptoms are dysmenorrhoea and infertility. Among women having had abdominal surgery for any gynecological reason, the prevalence of endometriosis is between 15% and 50%. Case report : We report the case of a 15 year-old patient who underwent surgery twice : once for appendicitis two years before and once for acute salpingitis and tubo-ovarian abscesses one year before. Laparotomy was performed by Pfannenstiel incision. The post operative course was uneventful. The patient reported the gradual emergence of two bluish nodes on the abdominal scar. These nodules became painful and turgid during the menstrual period. She also reported the issue of blood from the abdominal scar during menstruation. The abdominal examination, performed during the menstrual period, showed a scar of good quality and two regular shiny and bluish cutaneous nodules measuring 1 cm in size. These elements were firm and painless. An endometriosis node on the scar of laparotomy was suspected. Surgery was performed in order to remove both nodules. At surgery the depth of nodules reached the top of the abdominal fascia of the major rights. The content of these nodules was chocolate brown. The histo-pathological examination confirmed that these nodules contained ectopic endometrial tissue. Conclusion : The etiopathogeny of endometriosis is still a subject of debate. This case illustrates the possibility of occurrence of endometriosis on abdominal scars after laparotomy: an unusual location.

Arch Gynecol Obstet. 2010 Oct 30. [Epub ahead of print]

Beneficial effects of dienogest on uterine myoma volume: a retrospective controlled study comparing with gonadotropin-releasing hormone agonist.

Ichigo S, Takagi H, Matsunami K, Suzuki N, Imai A.

Department of Obstetrics and Gynecology, Matsunami General Hospital, Gifu, 501-6062, Japan.

PURPOSE: Uterine leiomyomas are the most common benign tumors of reproductive age women, but there is no effective medical therapy to data. Aim of this study was to examine and compare the efficacy of gonadotropin-releasing hormone agonist (GnRHa) versus dienogest in premenopausal women with uterine myoma.

METHODS: We retrospectively analyzed the medical records of 55 premenopausal patients with endometriosis, who received dienogest (2 mg daily) for 6 months regarding coexistence of uterine myoma between January 2008 and June 2010. To compare these data in a case-control study, we analyzed a matched control group of 12 patients treated with leuprolide acetate (1.88 mg monthly) for 6 months having uterine myoma.

RESULTS: Of the 55 patients treated with dienogest, six were associated with coexistent myoma node. Total myoma volume significantly decreased to 59.7 ± 7.0% of initial in dienogest group and 51.9 ± 5.5% in GnRHa group. Reduction rate in myoma volume was similar in both groups.

CONCLUSION: Uterine myoma volume was successfully reduced by use of dienogest. Consideration of GnRHa disadvantages may lead to short- or long-term management of women with myoma who are to be managed transiently, and who wish to avoid surgical intervention, especially perimenopausal women.

Mol Hum Reprod. 2010 Oct 28. [Epub ahead of print]

Pyrrolidine dithiocarbamate inhibits nuclear factor-{kappa}B pathway activation, and regulates adhesion, migration, invasion and apoptosis of endometriotic stromal cells.

Zhang JJ, Xu ZM, Zhang CM, Dai HY, Ji XQ, Wang XF, Li C.

Department of Obstetrics and Gynecology, Affiliated Hospital of Medical College of Qingdao University, Qingdao, Shandong, China.

The activation of nuclear factor-κB (NF-κB) has been implicated in the development and progression of endometriosis. The aim of this study is to investigate the potential application of pyrrolidine dithiocarbamate (PDTC), a potent NF-κB inhibitor, in the treatment of endometriosis. NF-κB-DNA binding activity, IκB phosphorylation and expression of nuclear p65 protein in endometriotic ectopic stromal cells (EcSCs), endometriotic eutopic stromal cells (EuSCs) and normal endometrial stromal cells (NESCs) were detected by electrophoretic mobility shift assay (EMSA) and Western Blot analysis. Adhesion, migration, invasion and apoptosis of EcSCs were observed by means of adhesion, migration, invasion and TUNEL assay respectively. Gene and protein expressions of CD44s, matrix metalloproteinase (MMP)-2, MMP-9 and survivin in EcSCs were measured by RT-PCR and Western Blot analysis. The results showed that PDTC in the absence or presence of interleukin (IL)-1β showed stronger inhibitory effects on NF-κB-DNA binding activity, IκB phosphorylation and expression of nuclear p65 protein in EcSCs than those in EuSCs or NESCs. PDTC enhanced apoptosis, and suppressed IL-1β-induced cellular adhesion, migration and invasion of EcSCs. Pretreatment of EcSCs with PDTC attenuated IL-1β-induced expressions of CD44s, MMP-2, MMP-9 and survivin at gene and protein levels. All these findings suggest that PDTC induces apoptosis and downregulates adhesion, migration and invasion of EcSCs through the suppression of various molecules. Therefore, PDTC could be used as a therapeutic agent for the treatment of endometriosis.

Appl Immunohistochem Mol Morphol. 2010 Oct 27. [Epub ahead of print]

Galectin-3 is Overexpressed in Various Forms of Endometriosis.

Noël JC, Chapron C, Borghese B, Fayt I, Anaf V.

*Department of Gynaecopathology, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium †Service de Gynécologie Obstétrique II and Reproductive Medecine, Université Paris Descartes, CHU Cochin, Saint Vincent de Paul, Paris, France.

Endometriosis is an enigmatic disease of unknown etiology and pathogenesis, which is defined as the presence of endometrial glands and stroma outside the uterus. The most widely accepted theory to explain endometriosis is probably the transplantation of an endometrial fragment during menstruation to ectopic sites, but the development of endometriosis is extremely complex and includes the adherence to the peritoneal surface and secondary invasion of the underlying tissues. In this study, we have investigated the potential role of galectin-3 (gal-3), a member of a group of carbohydrate-binding proteins, which plays a major role in cell adhesion, migration, angiogenesis, and invasion. The expression of gal-3 has been carried out by immunohistochemistry, according to the different phases of cycle in 50 cases of endometriosis (peritoneal endometriosis: n=10; ovarian endometriosis: n=10; deeply infiltrating endometriosis: n=30) and in 34 cases of eutopic endometrium (10 without endometriosis and 24 with endometriosis). In the proliferative and secretory phases of the cycle, the nuclear and membranous gal-3 expression was higher, first in each variant of the endometriosis than in the eutopic endometrium (P<0.05), and second in the eutopic endometrium of women with endometriosis than in eutopic endometrium of women without endometriosis. Our data suggest that gal-3 may have a potential role in the development of endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2010 Oct 27. [Epub ahead of print]

Comparison of aromatase inhibitor (letrozole) and immunomodulators (infliximab and etanercept) on the regression of endometriotic implants in a rat model.

Ceyhan ST, Onguru O, Fidan U, Ide T, Yaman H, Kilic S, Baser I.

Gülhane Military Medical Academy, Department of Obstetrics and Gynecology, GATA Medical School, Ankara, Turkey.

OBJECTIVE: Novel treatment strategies are needed in the treatment of endometriosis due to limited success rates with the currently available options. As inflammatory and immunological mechanisms have been shown to be involved in the mechanism of the disease, new modalities are likely to emerge. We investigated the effects of infliximab (INF), etanercept (ETA) and letrozole on the regression of experimental endometriosis.

STUDY DESIGN: In this experimental randomized trial, endometriosis was induced surgically in 44 adult female Sprague-Dawley rats. Establishment of implants was confirmed in 41 animals by a second operation on the 21st day. The rats were then randomly divided into four groups. Group I (n=10) served as controls. Group II (n=11) received letrozole (0.18mg/kg, i.p.), group III (n=10, i.p.) ETA (2.016mg/kg, i.p.), and group IV (n=10) INF (15.12mg/kg, i.p.) for a second 21-day period. Endometriotic implant size along with peritoneal fluid VEGF level and immunoreactivity were determined before and after the treatment in each group.

RESULTS: Endometriotic implant size reduced in all treatment groups. The effect of letrozole and ETA on implant size was similar but was significantly better than INF. Level of VEGF in peritoneal fluid did not change in any treatment group but post-treatment VEGF immunoreactivity was found significantly lower in the letrozole treated group.

CONCLUSIONS: Letrozole and ETA caused a regression on the implant size in experimental endometriosis. The only group with decreased VEGF expression was letrozole.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

J Clin Endocrinol Metab. 2010 Oct 27. [Epub ahead of print]

Polymorphism in Vitamin D-Binding Protein as a Genetic Risk Factor in the Pathogenesis of Endometriosis.

Faserl K, Golderer G, Kremser L, Lindner H, Sarg B, Wildt L, Seeber B.

Department of Gynecologic Endocrinology and Reproductive Medicine (K.F., L.W., B.S.), Division of Clinical Biochemistry (K.F., L.K., H.L.), and Department of Biological Chemistry (G.G.), Biocenter, and Innsbruck Medical University, A-6020 Innsbruck, Austria.

Context: Previous studies have implicated a deficiency in the inflammatory response in women who develop endometriosis. The specific immunological deficits have not been completely elucidated. Objective: Our objective was to identify differences in protein expression in serum that might shed light on the pathophysiology of endometriosis. Design and Setting: This cross-sectional study of women undergoing laparoscopy between 2003 and 2005 took place at a university medical center. Patients: Patients included consenting women age 18-49 yr undergoing surgery for pain and/or infertility or elective tubal ligation. Women with acute or chronic medical conditions were excluded. Intervention: Blood was collected preoperatively. Main Outcome Measure: Proteomic analysis of serum was done using two-dimensional difference gel electrophoresis. Results: We found 25 protein spots with a significant difference in abundance between women with endometriosis and controls, including acute-phase proteins and complement components. The abundance of vitamin D-binding protein was higher in all endometriosis pools by a factor of approximately 3 compared with the control pool (P < 0.02). Analysis of specific allele products using nano-scale liquid chromatography-electrospray ionization-mass spectrometry indicated that it was the GC*2 allele product that was in greater concentration in serum pools, as well as in single validation samples, in women with endometriosis (P = 0.006). In contrast to the GC*1 allele product, which is readily converted to a potent macrophage factor (Gc protein-derived macrophage-activating factor), the GC*2 allele product undergoes practically no such conversion. Conclusions: We speculate that the inability to sufficiently activate macrophages’ phagocytotic function in those carrying the GC*2 polymorphism (more prevalent in endometriosis) may allow endometriotic tissues to implant in the peritoneal cavity. Future studies evaluating specific vitamin D-binding protein polymorphisms as a risk factor for endometriosis in larger populations of women are warranted.

J Clin Gastroenterol. 2010 Oct 27. [Epub ahead of print]

Colonoscopic Findings and Histologic Diagnostic Yield of Colorectal Endometriosis.

Kim KJ, Jung SS, Yang SK, Yoon SM, Yang DH, Ye BD, Byeon JS, Myung SJ, Kim JH.

Department of Internal Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

BACKGROUND: No study has systematically investigated the colonoscopic findings and histologic diagnostic yield in the diagnosis of colorectal endometriosis.

OBJECTIVES: We classified the colonoscopic features of colorectal endometriosis and determined the diagnostic yield of endoscopic biopsy in relation to endoscopic subtypes of colorectal endometriosis.

METHODS: A total of 17 patients with colorectal endometriosis were assessed. The data from the colonoscopic and histologic assessments made between November 1994 and October 2009 were retrospectively analyzed in single tertiary referral teaching hospital.

RESULTS: Colonoscopy showed eccentric wall thickening in 14 patients (82%) and polypoid lesions in 3 patients (18%). Surface nodularities were noted in 11 of the 14 patients (79%) with eccentric wall thickening, and in 1 of the 3 patients (33%) with polypoid lesions. The overall histologic diagnostic yield was 47% (8 of the 17 patients). The rate of histologic confirmation was higher in patients with surface nodularities (8 of the 12 patients, 67%) versus those without (0 of the 5 patients, 0%) surface nodularities (P=0.02).

CONCLUSIONS: Eccentric wall thickening is the most common colonoscopic finding of colorectal endometriosis, and the histologic diagnostic yield of endoscopic biopsy is high when lesions are accompanied by surface nodularities.

Eur J Obstet Gynecol Reprod Biol. 2010 Oct 26. [Epub ahead of print]

Experimental endometriosis reduction in rats treated with Uncaria tomentosa (cat’s claw) extract.

Neto JN, Coelho TM, Aguiar GC, Carvalho LR, de Araújo AG, Girão MJ, Schor E.

Experimental Surgery Laboratory of the University Hospital of the Federal University of Maranhão, UFMA, São Luís (MA), Brazil; Gynecology Department, Pelvic Pain and Endometriosis Unit, Federal University of São Paulo/Escola Paulista de Medicina, São Paulo (SP), Brazil.

OBJECTIVE: The aim of this study was to analyze the macroscopic and histological changes that occur in experimental endometriosis after treatment with Uncaria tomentosa.

STUDY DESIGN: Experimental endometriosis was induced in twenty-five female Wistar rats. After three weeks, 24 animals developed grade III experimental endometriosis and were divided into two groups. Group “U” received U. tomentosa extract orally (32mg/day), and group “C” (control group) received a 0.9% sodium chloride solution orally (1ml/100g of body weight/day). Both groups were treated with gavage for 14 days. At the surgical intervention and after the animal was euthanized, the implant volume was calculated with the following formula: [4π (length/2)×(width/2)×(height/2)/3]. The autotransplants were removed, dyed with hematoxylin-eosin, and analyzed by light microscopy. The Mann-Whitney test was used for the independent samples, and the Wilcoxon test analyzed the related samples, with a significance level of 5%.

RESULTS: The difference between the initial average volumes of the autotransplants was not significant between the groups (p=0.18). However, the final average volumes were significantly different between the groups (p=0.001). There was a significant increase (p=0.01) between the initial and final average volumes in the control group, and treatment with the U. tomentosa caused a marked reduction in the growth over time (p=0.009). Histologically, in the experimental group (n=10) six rats had a well-preserved epithelial layer, three had mildly preserved epithelium, and one had poorly preserved epithelium. The epithelial layer occasionally presented sporadic epithelial cells. The control group (n=12) presented seven cases (58.3%) of well-preserved epithelial cells and five cases (41.7%) of mildly preserved epithelial cells.

CONCLUSIONS: Cat’s claw extract appears to be a promising alternative for treating endometriosis.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Reprod Sci. 2010 Oct 26. [Epub ahead of print]

Priorities for Endometriosis Research: A Proposed Focus on Deep Dyspareunia.

Vercellini P, Meana M, Hummelshoj L, Somigliana E, Viganò P, Fedele L.

Istituto Ostetrico e Ginecologico ”Luigi Mangiagalli,” Universita` degli Studi di Milano, Milan, Italy.

Women with endometriosis have a substantial increase in risk of deep dyspareunia with respect to the general female population of corresponding age. This symptom has personal and intimate implications, including unfavorable emotional impact in partners. Deep dyspareunia caused by endometriosis can be viewed as an originally visceral type of pain secondary to chronic inflammation (nociception) but with several superimposed components, including hyperalgesia, abnormal cortical perception, and psychological factors. Therefore, a simplistic biometric approach does not allow a comprehensive and elaborated assessment of the global impact of the symptom on women’s sexual function, psychological well-being, body-image, self-esteem, and relational adjustment. We suggest 10 specific issues to be addressed in future research on a clinically as well as scientifically neglected aspect of female health. Time has come to address this physically and psychologically distressing affliction without embarrassment and with a decidedly multidisciplinary perspective.

Nutr Res Rev. 2010 Oct 25:1-8. [Epub ahead of print]

Dietary therapy: a new strategy for management of chronic pelvic pain.

Sesti F, Capozzolo T, Pietropolli A, Collalti M, Bollea MR, Piccione E.

Endometriosis Center, Section of Gynecology and Obstetrics, Department of Surgical Sciences, Tor Vergata University Hospital, Rome, Italy.

Chronic pelvic pain (CPP) can be identified as a chronic nociceptive, inflammatory and neuropathic pain characterised by spontaneous pain and an exaggerated response to painful and/or innocuous stimuli. This pain condition is extremely debilitating and usually difficult to treat. Currently, the main approaches to treatment include counselling supported by reassuring ultrasound scanning or psychotherapy, attempting to provide reassurance using laparoscopy to exclude serious pelvic pathology, hormonal therapy and neuroablative treatment to interrupt nerve pathways. Dietary supplementation has been suggested as a means to treat chronic medical illnesses that are poorly responsive to prescription drugs or in which therapeutic options are limited, costly or carry a high side-effect profile. A comprehensive search of the PubMed database was performed using the search terms ‘chronic pelvic pain’, ‘oxidative stress’, ‘antioxidants’ and ‘dietary therapy’. The systematic review focuses on both randomised and non-randomised controlled trials from 2005 onwards, in which CPP was the end point. Given the complexity and not well-understood aetiology of CPP, its treatment is often unsatisfactory and limited to partial symptom relief. Dietary therapy with antioxidants improves function of the immune system and in fighting free radical damage. Agents with antioxidant activity are able to improve CPP without undesired effects and any important metabolic changes associated with hormonal suppression therapy. In conclusion, dietary therapy with antioxidants could be considered as a new effective strategy in the long term for CPP, and may be better accepted by patients. Further randomised trials with larger series and long-term follow-up to confirm these observations are needed.

Photomed Laser Surg. 2010 Oct 22. [Epub ahead of print]

Studies on Function of P-Glycoprotein in Photodynamic Therapy of Endometriosis.

Wołuń-Cholewa M, Szymanowski K, Andrusiewicz M, Warchoł W.

1 Department of Cell Biology, Poznan University of Medical Sciences , Poznań, Poland .

Abstract Objective: The aim of the present study was to examine whether the effects of endometriosis-targeted photodynamic therapy (PDT), dependent on 5-aminolevulinic acid (ALA), rely on the presence of P-glycoprotein (P-gp), which is regarded as constituting one of the causes of multidrug resistance phenomenon. Background: The significance of the undertaken studies reflects the complete absence of reports related to the modulation of P-gp activity and efficacy of PDT in patients with endometriosis. Materials and Methods: Tissue samples of normal endometria were obtained from eight women after hysterectomy who were diagnosed with cervical intra-epithelial neoplasia. Fragments of ovarian endometriosis were obtained from 15 women. Epithelial cells were isolated from the material and in in vitro conditions were preincubated with P-gp blocker-verapamil-before ALA-PDT. The cytotoxicity was evaluated using the XTT test, allowing us to estimate cell growth inhibition. Statistical analysis of the results involved the nonparametric Wilcoxon paired rank test and the Mann-Whitney U-test using the Statistica v5 software (p < 0.05). In parallel, P-gp presence in the analyzed material was evaluated using immunohistochemistry. Results: In normal endometrial epithelium, verapamil was shown to intensify phototoxic effects at 2 and 4 mmol/L ALA (p < 0.05). In endometriotic epithelium, such intensification was noted in all examined concentrations of ALA (p < 0.001). Moreover, the ectopic epithelial cells were more sensitive than eutopic epithelial cells to PDT upon ALA alone, as well as after preincubation with verapamil. Immunohistohemical analysis allowed us to demonstrate the absence of glycoprotein P in normal endometrium. In endometriosis, P-gp was localised in both the epithelium and the stroma of the examined material. Conclusion: Phototoxic effects could be amplified in epithelial cells of endometriotic foci by appropriate action of verapamil and 5-aminolevulinic acid.

Eur J Obstet Gynecol Reprod Biol. 2010 Oct 21. [Epub ahead of print]

Do patients manage to achieve pregnancy after a major complication of deeply infiltrating endometriosis resection?

Kondo W, Daraï E, Yazbeck C, Panel P, Tamburro S, Dubuisson J, Jardon K, Mage G, Madelenat P, Canis M.

CHU de Clermont-Ferrand, Polyclinique de l’Hôtel Dieu, Clermont-Ferrand, France; Department of Obstetrics and Gynecology, Boulevard Léon Malfreyt 63058 Clermont Ferrand Cédex 1, France.

OBJECTIVE: To evaluate the fertility status in women suffering from major postoperative complications following deep endometriosis surgery.

STUDY DESIGN: A retrospective study in teaching and research hospitals (tertiary centers) including 23 women submitted to the surgical treatment for deep endometriosis and presenting a major postoperative complication. Postoperatively, women desiring pregnancy who conceived were compared to those who did not conceive using Mann-Whitney test and Fisher’s exact test. Main outcome measure included the pregnancy rate among these women.

RESULTS: The overall intrauterine pregnancy rate was 47.8% and the live birth rate was 30.4%. There were 10 spontaneous conceptions and 3 IVF conceptions among 11 patients. Women who did not conceive were older than those who conceived (33.9 vs. 29.3 years; p=0.02). The pregnancy rate after intestinal complications was lower than after urinary complications (33.3% vs. 83.3%; p=0.04).

CONCLUSION: Fertility remains preserved among women experiencing a major complication after removal of deep endometriosis with a live birth rate of 30.4%. Women experiencing bowel complications have a reduced probability of conception compared with those who experience a urologic complication.

Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Fertil Steril. 2010 Oct 21. [Epub ahead of print]

In vitro effects of peroxisome proliferator-activated receptor-γ ligands on gene expression in lipopolysaccharide-induced endometrial and endometriotic stromal cells.

Sharma I, Dhawan V, Saha SC, Dhaliwal LK.

Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

This in vitro study demonstrates the comparative anti-inflammatory effects of rosiglitazone and 15d-PGJ(2) in endometriosis and provides evidence for exploitation of peroxisome proliferator-activated receptor-γ as a therapeutic target.

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

Reprod Biol Endocrinol. 2010 Oct 21;8:123.

TRIzol treatment of secretory phase endometrium allows combined proteomic and mRNA microarray analysis of the same sample in women with and without endometriosis.

Fassbender A, Simsa P, Kyama CM, Waelkens E, Mihalyi A, Meuleman C, Gevaert O, Van de Plas R, de Moor B, D’Hooghe TM.

Leuven University Fertility Centre, Department of Obstetrics & Gynaecology, University Hospital Gasthuisberg, Leuven, Belgium. thomas.dhooghe@uzleuven.be.


BACKGROUND: According to mRNA microarray, proteomics and other studies, biological abnormalities of eutopic endometrium (EM) are involved in the pathogenesis of endometriosis, but the relationship between mRNA and protein expression in EM is not clear. We tested for the first time the hypothesis that EM TRIzol extraction allows proteomic Surface Enhanced Laser Desorption/Ionisation Time-of-Flight Mass Spectrometry (SELDI-TOF MS) analysis and that these proteomic data can be related to mRNA (microarray) data obtained from the same EM sample from women with and without endometriosis.

METHODS: Proteomic analysis was performed using SELDI-TOF-MS of TRIzol-extracted EM obtained during secretory phase from patients without endometriosis (n = 6), patients with minimal-mild (n = 5) and with moderate-severe endometriosis (n = 5), classified according to the system of the American Society of Reproductive Medicine. Proteomic data were compared to mRNA microarray data obtained from the same EM samples.

RESULTS: In our SELDI-TOF MS study 32 peaks were differentially expressed in endometrium of all women with endometriosis (stages I-IV) compared with all controls during the secretory phase. Comparison of proteomic results with those from microarray revealed no corresponding genes/proteins.

CONCLUSION: TRIzol treatment of secretory phase EM allows combined proteomic and mRNA microarray analysis of the same sample, but comparison between proteomic and microarray data was not evident, probably due to post-translational modifications.

Ann Diagn Pathol. 2010 Oct 20. [Epub ahead of print]

Carcinoma of müllerian origin presenting as colorectal cancer: a clinicopathologic study of 13 Cases.

Yang Q, Wang H, Cho HY, Jung SJ, Kim KR, Ro JY, Shen SS.

Department of Pathology, Three Gorges University, Hubei, People’s Republic of China.

Carcinomas of müllerian origin involving colorectum in women with no concurrent or history of gynecologic malignancies are diagnostically challenging, and its histogenetic origin is uncertain. We reviewed 13 cases of carcinoma of müllerian origin with clinical presentation mimicking primary colorectal carcinoma. The patients’ average age was 63.9 years. All except 2 patients presented with mass lesions in rectosigmoid colon or rectovaginal septum. The major presenting symptoms were rectal bleeding (4/13), rectosigmoid mass (6/13), vaginal mass (1/13), and abdominal pain or constipation (2/13). The average size of tumor was 4.2 cm (range, 2.4-15.0 cm). Among the 10 patients who underwent preoperative biopsy, 5 were diagnosed to have moderately and poorly differentiated colorectal carcinoma. All tumors were surgically resected with final diagnoses of moderately differentiated endometrioid carcinoma in 6 cases, mixed serous and endometrioid carcinoma in 4 cases, malignant mixed müllerian tumor in 2 cases, and undifferentiated carcinoma in 1 case. In 9 of 13 cases, foci of endometriosis were identified adjacent to or within the tumor. One case had endosalpingiosis. Immunohistochemical stains showed, after positive results, the following: cytokeratin 7 (CK7; 13/13), estrogen receptor (13/13), progesterone receptor (10/13), cytokeratin 20 (CK20; 0/13), and CDX-2 (0/13). In conclusion, carcinoma of müllerian origin often presents as bulky mass in rectosigmoid or rectovaginal septum clinically mimicking primary colorectal cancer. Endometriosis might be an important etiologic factor. Familiarities of this unusual clinicopathologic entity, careful morphologic evaluation, and immunohistochemical stain with a panel of markers (CK7, CK20, estrogen receptor, progesterone receptor, CDX-2) will be helpful for the correct diagnosis.

Copyright © 2010 Elsevier Inc. All rights reserved.

Colorectal Dis. 2010 Oct 19. doi: 10.1111/j.1463-1318.2010.02457.x. [Epub ahead of print]

Is routine histopathological examination of appendectomy specimens useful? A systematic review of the literature.

Swank H, Eshuis E, Ubbink D, Bemelman W.

Department of Surgery, Academic Medical Centre, Amsterdam . Department of Clinical Epidemiology . & Biostatistics and Surgery, Academic Medical Centre, Amsterdam.

Histopathological examination of the appendix after appendectomy is Aim routinely performed. The object of this systematic review is to determine whether routine histopathological examination of the appendix is justified on  PubMed, EMBASE, Web of Science and the Cochrane library grounds of cost. Method were searched without language restriction up to October 1 2009. All articles that reported on the incidence of histopathologically proven aberrant  19 case series reported the appendiceal pathology were included. Results incidence of a benign neoplasm (0.5%, weighted mean (WM)), malignant neoplasm (0.2%, WM) and other pathology (0-14%). Nine articles reported the sensitivity of the intraoperative findings to detect aberrant diagnoses. Parasitic infection was detected in 0-19%, endometriosis in 0% and granulomatosis in 0-11% of cases. Five articles addressed the consequences of aberrant pathology. Most patients with parasite infection, granulomatosis and malignant neoplasms underwent additional investigation or treatment, in contrast to patients with a benign  The incidence of unexpected findings in appendectomy neoplasm. Conclusion specimens is low and the intraoperative diagnosis alone appears insufficient for identifying unexpected disease. The benefit of histopathology is studied inadequately. From the present available evidence routine histopathology cannot be judged as useless.

Copyright © 2010 The Association of Coloproctology of Great Britain and Ireland.

Hum Reprod Update. 2010 Oct 19. [Epub ahead of print]

The role of mast cells and their mediators in reproduction, pregnancy and labour.

Menzies FM, Shepherd MC, Nibbs RJ, Nelson SM.

Centre for Population and Health Science, College of Medicine , Veterinary and Life Sciences University of Glasgow, McGregor Building, Floor 2, Western Infirmary, Glasgow, UK.

BACKGROUND Mast cells (MCs) are the classical mediators of allergy, however, their importance in the development of innate and adaptive immune responses is increasingly being recognized. Herein, the present MC literature is summarized, with particular focus on studies of MCs in the endometrium and myometrium, and their involvement in fertility, implantation, pregnancy and labour. METHODS Recent developments in MC biology were identified by systematic searches of PubMed, Medline and Google Scholar from 2000 to November 2009. To specifically examine the role of MCs in fertility and pregnancy, we then performed a systematic review of English literature cited in the PubMed, Medline and Google Scholar databases, but extended the search period, from 1980 to January 2010 RESULTS MCs can respond to immunoglobulin E-independent innate immune stimuli and are present within the endometrium, with activation and release of mediators occurring prior to menstruation and in association with endometriosis. With respect to pregnancy, MCs are redundant during blastocyst implantation and although their mediators can induce myometrial contractility, there is no epidemiological link of preterm birth with allergy, suggesting a non-essential role or robust regulation. In males, MCs are present in the testes and are increased in oligo- and azoospermia, with MC mediators directly suppressing sperm motility in a potentially reversible manner. CONCLUSIONS MCs are prevalent in the female and male reproductive tract. However, whether MCs are absolutely required for a successful pregnancy or are fundamental to reproductive pathology, and thereby a therapeutic target, remains to be determined.

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