2011 Mar 31. [Epub ahead of print]

Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine: a new technique.

Canis M, Manhes H, Mage G.

Source

Department of Gynecologic Surgery, CHU Estaing, Clermont-Ferrand, France.

Gynecol Oncol. 2011 Mar 30. [Epub ahead of print]

Primary repair of rectovaginal fistulas complicating pelvic surgery by gracilis myocutaneous flap.

Nassar OA.

Abstract

OBJECTIVES:

Complex rectovaginal fistulas repair are extremely challenging. Various surgical options have been suggested; nevertheless, none had been universally accepted as the procedure of choice. This prospective study discusses a novel surgical technique using gracilis myocutaneous flap interposition.

METHODS:

Eleven patients had fistulas post-resection of pelvic malignancy (n=10) and rectal endometriosis (n=1). Primary treatment was pelvic resection; nevertheless, 6 cases had adjuvant chemo-irradiation, 2 cases had post-operative irradiation and 2 patients had chemotherapy only. Fistulas mean diameter was 2±0.24 cm (1-3) and 8 patients (72.7%) had their fistulas in the middle vaginal third. Repair was wide debridement of fistulas margins followed by gracilis myocutaneous flap interposition with synchronous diverting stomas. Success was defined as healing of fistula after stomal closure.

RESULTS:

Five patients were repaired by single gracilis myocutaneous flaps, 2 cases by simple gracilis muscle and 4 cases by double gracilis myocutaneous flaps. Patients had a mean follow-up time of 34.8±5.03 months (12-67) and all patients had definitive healing of their fistulas (100%). Median time to stoma closure was 2 months (1-5). Four women (36.4%) had at least one early postoperative complications including temporary leak (n=3), vaginal sepsis (n=1), partial skin paddle necrosis (n=1) and donor limb deep venous thrombosis (n=1). Late morbidities were seen in 3 cases (27.3%) including vaginal stricture, anorectal anastomotic stricture and anastomotic tumor recurrence.

CONCLUSION:

Rectovaginal septum repair requires adequate debridement of necrotic devascularized tissues, tissue transposition and reconstruction of vaginal wall. Gracilis myocutaneous flaps are ideal for this issue.

Mol Hum Reprod. 2011 Mar 30. [Epub ahead of print]

Urocortin2 and urocortin 3 in endometriosis: evidence for a possible role in inflammatory response.

Novembri R, Carrarelli P, Toti P, Rocha AL, Borges LE, Reis FM, Piomboni P, Florio P, Petraglia F.

Source

Department of Pediatrics, Obstetrics and Reproductive Medicine, Section of Obstetrics and Gynecology, University of Siena, Siena, Italy and.

Abstract

Urocortins 2 (Ucn2) and urocortin 3 (Ucn3) are neuropeptides expressed by human endometrium. This study evaluated a) the expression of Ucn2 and Ucn3 mRNA in endometriotic lesions and in endometrium of women with endometriosis; b) the effect of Ucn2 and Ucn3 on cytokines secretion from cultured endometrial stromal cells. Endometriotic tissue was collected from endometrioma (n=39); endometrial specimens were obtained from women with (n=39) and without (n=41) endometriosis throughout menstrual cycle. Tissue specimens were analyzed for Ucn2 and Ucn3 mRNA expression and peptide localization; the effects of Ucn2 or Ucn3 on tumour necrosis factor (TNF-a) and interleukin (IL-4) secretion from cultured endometrial stromal cells was studied. Ucn2 and Ucn3 mRNA expression and localization were assessed by RT-PCR and by immuohistochemistry respectively; cytokines secretion were measured by ELISA. Results showed that endometriotic tissue expressed both Ucn2 and Ucn3, with Ucn3 expression higher in ectopic than in eutopic endometrium. Endometrial Ucn2 mRNA expression in controls showed peak values at early proliferative phase, while in endometriotic patients low expression and no significant changes throughout menstrual cycle were observed. Endometrial Ucn3 mRNA expression was highest in late secretory phase in controls, while in endometriotic patients low levels and no menstrual cycle related changes were found. When added to cultured endometrial cell cultures, Ucn2 significantly increased TNF-α (p<0.01) and IL-4 (p<0.001), while Ucn3 induced an increase of IL-4 secretion (p<0.01). In conclusion, endometriotic tissue expressed and localized Ucn2 and Ucn3; patients with endometriosis showed Ucn2 and Ucn3 mRNA expression in eutopic endometrium lower than in control group, with no endometrial cycle-related changes. Ucn2 and Ucn3 modulated TNF-α and IL-4 secretion from culture endometrial cells. These data suggest a possible involvement of Ucn2 and Ucn3 in the mechanisms of endometriosis.

Acta Radiol. 2011 Mar 28. [Epub ahead of print]

Mixed endometrioid and serous carcinoma developing in abdominal wall endometriosis following Cesarean section.

Da Ines D, Bourdel N, Charpy C, Montoriol PF, Petitcolin V, Canis M, Garcier JM.

Source

Department of Radiology and Medical Imaging.

Abstract

Abdominal wall endometriosis is unusual and mostly occurs in scars following Cesarean section. Although malignant transformation is rare, it must be recognized in order to benefit from radical resection. We report a very rare case of mixed endometrioid and serous carcinoma developing in a Cesarean section endometriosis scar and the way we managed it using surgery and chemotherapy. 18-FDG PET-CT imaging was performed to correctly stage the disease.

Curr Drug Targets. 2011 Mar 28. [Epub ahead of print]

FOXO Transcription Factors and their Role in Disorders of the Female Reproductive Tract.

Christian M, Lam EW, Wilson MS, Brosens JJ.

Source

Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Campus, London W12 0NN, UK. j.brosens@imperial.ac.uk.

Abstract

All fundamental reproductive events in the human ovary and uterus, including ovulation, implantation and menstruation, are dependent upon profound tissue remodelling, characterized by cyclical waves of cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown and regeneration. Although the rise and fall in ovarian hormones, estradiol and progesterone, orchestrate these reproductive events, FOXO transcription factors, an evolutionary conserved subfamily of forkhead transcription factors, have emerged major downstream effector molecules, capable of integrating hormonal cues with a variety of stress, growth factor and cytokine signal transduction pathways. The ability of FOXOs to regulate seemingly opposing cellular responses, ranging from cell cycle arrest and oxidative stress responses to differentiation and apoptosis, renders these transcription factors indispensable for cyclic tissue remodelling in the reproductive tract. Aberrant expression or perturbed activity of FOXO transcription factors are increasingly linked to prevalent reproductive disorders, such as endometriosis, endometrial cancer, primary ovarian insufficiency and pregnancy failure, which in turn highlights their potential as therapeutic targets.

J Clin Periodontol. 2011 Mar 28. doi: 10.1111/j.1600-051X.2011.01720.x. [Epub ahead of print]

Periodontal status of males attending an in vitro fertilization clinic.

Klinger A, Hain B, Yaffe H, Schonberger O.

Source

Department of Periodontics, Hebrew University and Hadassah Faculty of Dental Medicine, Jerusalem, Israel IVF Unit, Department of Obstetrics and Gynaecology, Bikur Cholim Hospital, Jerusalem, Israel.

Abstract

Klinger A, Hain B, Yaffe H, Schonberger O. Periodontal status of males attending an in vitro fertilization clinic. J Clin Peridontol 2011; doi: 10.1111/j.1600-051X.2011.01720.x. ABSTRACT: Aims: An association has been demonstrated previously between periodontal diseases and various systemic conditions, including endometriosis. A possible role of dental infection in male infertility was also suggested. The aim of the present study was to examine the association between fertility parameters and the periodontal status of men attending a fertility and in vitro fertilization (IVF) clinic. Methods: The study population consisted of 75 men attending the clinic for sperm analysis before homologue semen insemination or IVF. The quality of sperm was assessed according to WHO criteria. On the same day, patients received a clinical periodontal examination. Results: The patients were diagnosed with either gingivitis (40%) or periodontitis (48%), whereas the remaining 12% were classified as “periodontally healthy”. Normospermia was attributed to 37%, oligozoospermia to 48% and azoospermia to 15% of these patients. Familial infertility was significantly associated with having at least one WHO parameter contributing to infertility. A higher number of sites with deep periodontal pockets tended to associate positively with sperm sub-motility. Clinical attachment levels were significantly associated with sperm sub-motility. Conclusions: These findings may point to a possible association between male infertility, diminished semen quality and periodontal infections in men attending fertility and IVF clinics.

Hum Reprod. 2011 Mar 25. [Epub ahead of print]

Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model.

Colette S, Defrère S, Lousse JC, Van Langendonckt A, Gotteland JP, Loumaye E, Donnez J.

Source

Université Catholique de Louvain, Institut de Recherche Expérimentale et Clinique, Department of Gynecology, Cliniques Universitaires St Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium.

Abstract

BACKGROUND Steroid sulfatase (STS) is involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium of disease-free and endometriosis patients. The present study was designed to investigate its role in endometriosis development. METHODS Human endometrial explants were cultured on inserts for 24 h to assess the effectiveness of an STS inhibitor (STS-I), estradiol-3-O-sulfamate (E2MATE), on STS activity in endometrial tissue. Endometriosis was induced in mice, and E2MATE (or vehicle alone) was given orally for 21 days. Plasma estradiol levels were measured, and STS activity was assessed in murine organs (uterus, liver and leukocytes) and in lesions. Lesion number, weight and size (morphometry) were quantified. Lesion STS and progesterone receptor (PR) expression, proliferation and apoptosis rates were determined by immunohistochemistry. RESULTS In vitro, addition of 1 µM E2MATE to the culture medium resulted in decreased STS activity in endometrial explants (P < 0.001). Treatment of mice with E2MATE (1.0 and 0.5 mg/kg) did not modify plasma estradiol levels, but inhibited STS activity in murine uterus (P < 0.05), liver (P < 0.001) and leukocytes (P < 0.001), as well as in induced lesions (P < 0.05). E2MATE reduced lesion weight (P < 0.01) and size (P < 0.05), but had no impact on proliferation or apoptosis rates, nor STS protein expression. Stromal edema was observed in the uterus of animals treated with E2MATE, but not in the stroma of lesions. Increased PR expression was detected in endometriotic lesions (P < 0.001). CONCLUSIONS E2MATE was shown to effectively inhibit STS activity in endometrial tissue in vitro. In vivo, E2MATE decreased endometriosis development without affecting systemic estradiol levels. Use of STS-I could therefore be of potential interest in endometriosis treatment.

Hum Reprod. 2011 Mar 25. [Epub ahead of print]

Oral contraceptives and endometriosis.

Roman H.

Source

Department of Obstetrics and Gynecology, Groupe de Recherche EA 4308 ‘Spermatogenesis and Male Gamete Quality’, Rouen University Hospital, 1 rue de Germont, 76031 Rouen, France.

Int Urogynecol J Pelvic Floor Dysfunct. 2011 Mar 24. [Epub ahead of print]

Enlarging perineal endometrioma developing after colpoperineorrhaphy.

Strube FA, Niazi M, Lazarou G.

Source

Department of Obstetrics and Gynecology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY, USA.

Abstract

Although endometriosis is not infrequent, the occurrence of perineal endometriomata is relatively rare and is generally attributed to seeding of endometrial cells to the perineal body during obstetrical trauma. A 45-year-old female with a history of a colpoperineorrhaphy during menses and a remote history of obstetric perineal trauma presented with an enlarging perineal mass. Excision of the mass led to a clinical and histopathologic diagnosis of perineal endometriosis. Elective surgery disrupting the vaginoperineal epithelium performed during menses may facilitate the seeding of endometrial cells to the perineal body and formation of perineal endometriomata.

J Ethnopharmacol. 2011 Mar 24;134(2):373-8. Epub 2010 Dec 25.

Combining rigour with relevance: a novel methodology for testing Chinese herbal medicine.

Flower A, Lewith G, Little P.

Source

Department of Primary Care, Southampton Medical School, University of Southampton, UK. flower.power@which.net

Abstract

BACKGROUND:

There is a need to develop an evidence base for Chinese herbal medicine (CHM) that is both rigorous and reflective of good practice. This paper proposes a novel methodology to test individualised herbal decoctions using a randomised, double blinded, placebo controlled clinical trial.

METHOD:

A feasibility study was conducted to explore the role of CHM in the treatment of endometriosis. Herbal formulae were pre-cooked and dispensed as individual doses in sealed plastic sachets. This permitted the development and testing of a plausible placebo decoction. Participants were randomised at a distant pharmacy to receive either an individualised herbal prescription or a placebo.

RESULTS:

The trial met the predetermined criteria for good practice. Neither the participants nor the practitioner-researcher could reliably identify group allocation. Of the 28 women who completed the trial, in the placebo group (n=15) 3 women (20%) correctly guessed they were on placebo, 8 (53%) thought they were on herbs and 4 (27%) did not know which group they had been allocated to. In the active group (n=13) 2 (15%) though they were on placebo, 8 (62%) thought they were on herbs and 3 (23%) did not know. Randomisation, double blinding and allocation concealment were successful and the study model appeared to be feasible and effective.

CONCLUSION:

It is now possible to subject CHM to rigorous scientific scrutiny without compromising model validity. Improvement in the design of the placebo using food colourings and flavourings instead of dried food will help guarantee the therapeutic inertia of the placebo decoction.

Mol Endocrinol. 2011 Mar 24. [Epub ahead of print]

Functional MicroRNA Involved in Endometriosis.

Hawkins SM, Creighton CJ, Han DY, Zariff A, Anderson ML, Gunaratne PH, Matzuk MM.

Source

Departments of Obstetrics and Gynecology (S.M.H., M.L.A.), Medicine (C.J.C.), Pathology and Immunology (D.Y.H., P.H.G., M.L.A., M.M.M.), Molecular and Cellular Biology (M.M.M.), and Molecular and Human Genetics (M.M.M.) and the Dan L. Duncan Cancer Center (S.M.H., C.J.C., A.Z., M.L.A., M.M.M.), Baylor College of Medicine, Houston, Texas 77030; and Department of Biology and Biochemistry (P.H.G.), University of Houston, Houston, Texas 77204.

Abstract

Endometriosis is a common disease seen by gynecologists. Clinical features involve pelvic pain and unexplained infertility. Although endometriosis is pathologically characterized by endometrial tissue outside the normal uterine location, endometriosis is otherwise not easily explained. Endometriomas, endometriotic cysts of the ovary, typically cause pain and distortion of pelvic anatomy. To begin to understand the pathogenesis of endometriomas, we describe the first transcriptome-microRNAome analysis of endometriomas and eutopic endometrium using next-generation sequencing technology. Using this approach, we generated a total of more than 54 million independent small RNA reads from our 19 clinical samples. At the microRNA level, we found 10 microRNA that were up-regulated (miR-202, 193a-3p, 29c, 708, 509-3-5p, 574-3p, 193a-5p, 485-3p, 100, and 720) and 12 microRNA that were down-regulated (miR-504, 141, 429, 203, 10a, 200b, 873, 200c, 200a, 449b, 375, and 34c-5p) in endometriomas compared with endometrium. Using in silico prediction algorithms, we correlated these microRNA with their corresponding differentially expressed mRNA targets. To validate the functional roles of microRNA, we manipulated levels of miR-29c in an in vitro system of primary cultures of human endometrial stromal fibroblasts. Extracellular matrix genes that were potential targets of miR-29c in silico were significantly down-regulated using this biological in vitro system. In vitro functional studies using luciferase reporter constructs further confirmed that miR-29c directly affects specific extracellular matrix genes that are dysregulated in endometriomas. Thus, miR-29c and other abnormally regulated microRNA appear to play important roles in the pathophysiology of uterine function and dysfunction.

Am J Epidemiol. 2011 Mar 23. [Epub ahead of print]

Bilateral Oophorectomy in Relation to Risk of Postmenopausal Breast Cancer: Confounding by Nonmalignant Indications for Surgery?

Nichols HB, Visvanathan K, Newcomb PA, Hampton JM, Egan KM, Titus-Ernstoff L, Trentham-Dietz A.

Abstract

Bilateral oophorectomy is often performed during hysterectomy for benign conditions and can reduce breast cancer risk by 20%-50% when performed at younger ages. Accuracy of estimating the decrease in breast cancer risk associated with bilateral oophorectomy could be affected by common conditions that lead to surgery, such as uterine fibroids or endometriosis. The authors examined the potential for confounding by nonmalignant indications for surgery on breast cancer risk estimates in a population-based case-control study of invasive breast cancer newly diagnosed in 1992-1995. Breast cancer cases (N = 4,935) aged 50-79 years were identified from Wisconsin, Massachusetts, and New Hampshire tumor registries; similarly aged controls (N = 5,111) were selected from driver’s license and Medicare lists. Reproductive and medical history was obtained from structured telephone interviews. Odds ratios and 95% confidence intervals were estimated with multivariate logistic regression. Women who underwent bilateral oophorectomy with hysterectomy at age ≤40 years had significantly reduced odds of breast cancer (odds ratio = 0.74, 95% confidence interval: 0.60, 0.90) compared with women with intact ovaries and uterus. Effect estimates were virtually unchanged after adjustment for uterine fibroids or endometriosis history. Results indicate that breast cancer risk reductions conferred by bilateral oophorectomy are not strongly confounded by failure to account for nonmalignant indications for surgery.

Genet Mol Res. 2011 Mar 22;10(1):465-70.

RsaI polymorphism of the ERβgene in women with endometriosis.

Silva RC, Costa IR, Bordin BM, Silva CT, Souza SR, Júnior CL, Frare AB, Moura KK.

Source

Núcleo de Pesquisas Replicon, Pontifícia Universidade Católica de Goiás, Goiânia, GO, Brasil ritagenetica@yahoo.com.br.

Abstract

We examined the frequency of RsaI polymorphism of the ERβgene in 54 patients diagnosed with endometriosis and 46 controls. Peripheral blood was collected from women undergoing laparoscopy with a confirmed diagnosis of endometriosis. Polymorphisms of the ERβgene and p53 were assessed by PCR and analyzed on 2% agarose gel stained with ethidium bromide. The AG polymorphism genotype frequency in patients with endometriosis was 59.3%, with 40.7% GG. In the control group, the frequency of AG was 6.5%, with 93.5% GG. The frequency of heterozygous AG was nine times higher in patients with endometriosis than in the control group (P < 0.0001).

Hum Reprod. 2011 Mar 22. [Epub ahead of print]

Laparoscopic sigmoid resection with transrectal specimen extraction: a novel technique for the treatment of bowel endometriosis.

Wolthuis AM, Meuleman C, Tomassetti C, D’Hooghe T, Fieuws S, Penninckx F, D’Hoore A.

Source

Department of Abdominal Surgery, University Hospital Leuven, Herestraat 49, 3000 Leuven, Belgium.

Abstract

BACKGROUND Multidisciplinary laparoscopic treatment is the standard of care for radical treatment of deep infiltrating pelvic endometriosis. If bowel resection is necessary, a muscle-split or Pfannenstiel incision is also required. The avoidance of any laparotomy could decrease surgical stress response, give a faster return to normal bowel function, decrease post-operative pain and reduce wound complications and incisional hernias. We assessed post-operative outcome after a full laparoscopic sigmoid resection for bowel endometriosis. PATIENTS AND METHODS Twenty-one patients who underwent elective full laparoscopic sigmoid resection for bowel endometriosis from September 2009 to September 2010 were matched for age, American Society of Anesthesiologists class and BMI to 21 patients who underwent a conventional laparoscopic sigmoid resection. Groups were compared for peri-operative factors, complications, length of hospital stay, post-operative pain (Visual Analog Scale: VAS), analgesics consumption and inflammatory response (plasma C-reactive protein: CRP). RESULTS Median operating time was 15 min shorter with transrectal specimen extraction (P = 0.003). VAS-scores and use of analgesics were higher in the conventional laparoscopic group (P = 0.0005). Mean CRP-level tended to be higher in the transrectal specimen extraction group (38%, P = 0.054) but there was no difference in increase in CRP level between groups (P = 0.15). There were no anastomotic leaks or reinterventions in either group, and the median hospital stay was similar. At follow-up, no wound infections or incisional hernias were observed and no patients reported anal dysfunction. CONCLUSION Full laparoscopic sigmoid resection reduced operating times and decreased post-operative VAS-scores and analgesic requirements compared with the conventional laparoscopic sigmoid resection for bowel endometriosis.

Eur J Obstet Gynecol Reprod Biol. 2011 Mar 21. [Epub ahead of print]

Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility.

Szczepańska M, Mostowska A, Wirstlein P, Lianeri M, Marianowski P, Skrzypczak J, Jagodziński PP.

Source

Department of Obstetrics, Gynecology and Gynecological Oncology, Division of Reproduction, Poland.

Abstract

OBJECTIVE:

Endometriosis has been considered an epigenetic disease. Single nucleotide polymorphisms (SNPs) located in genes encoding enzymes of the folate and choline metabolism may affect DNA methyltransferase activity.

STUDY DESIGN:

We studied 16 SNPs in 12 folate and choline metabolism genes, including BHMT (rs7356530 and rs3733890), BHMT2 (rs625879), CBS (844ins68), CHDH (rs893363 and rs2289205), CHKA (rs7928739), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394), PCYT1A (rs712012 and rs7639752), PEMT (rs4244593 and rs4646406) and TCN (rs1801198) in one hundred and sixty-three infertile women with minimal endometriosis and one hundred and fifty fertile women.

RESULTS:

There were no significant differences between genotype and allele frequencies of these gene variants in infertile women with endometriosis (n=163) and controls (n=150). The lowest, but not statistically significant, p values of the trend test were observed for the CBS 844ins68 and MTR rs1805087 (p(trend)=0.0527 and p(trend)=0.0771, respectively) polymorphisms. However, the exhaustive multifactor dimensionality reduction analysis revealed an epistatic interaction between rs1801133 of MTHFR and rs4244593 of PEMT in endometriosis-associated infertility (p=0.0240).

CONCLUSIONS:

Our results showed moderate evidence for the contribution of SNPs located in genes encoding folate and choline metabolism enzymes to infertility in women with endometriosis.

Gynecol Oncol. 2011 Mar 21. [Epub ahead of print]

No benefit from combining HE4 and CA125 as ovarian tumor markers in a clinical setting.

Jacob F, Meier M, Caduff R, Goldstein D, Pochechueva T, Hacker N, Fink D, Heinzelmann-Schwarz V.

Source

Translational Research Group, University Hospital Zurich, Switzerland.

Abstract

OBJECTIVE:

About 70% of epithelial ovarian cancer patients (EOC) are diagnosed at advanced stage with a five-year survival rate of only 30%. Whilst CA125 detects peritoneally-spread disease, it has limited sensitivity for early cancers, many of which are potentially curable.

METHODS:

We compared the new commercially available tumor marker HE4 with CA125 individually, in combination, within the risk of malignancy index (RMI) and the newly defined risk of malignancy algorithm (ROMA). Our prospectively-collected cohort of 160 patients consisted of healthy controls, benign diseases, and borderline tumors/adenocarcinomas of ovarian, tubal, peritoneal and endometrial origin. HE4 and CA125 were measured in serum using standardized ELISA.

RESULTS:

Both markers showed similar diagnostic performance in the detection of EOC at clinically defined thresholds (CA125 35U/ml; HE4 70pM) but HE4 was not elevated in endometriosis. Comparison of non-malignant diagnoses (n=71) versus early stage ovarian and tubal cancers (n=19) revealed that HE4 and ROMA displayed the best diagnostic performance (AUC 0.86/0.87, specificity 85.9%/87.3% and sensitivity 78.9%/78.9%, respectively). Whilst RMICA125 detects peritoneal cancer better than all other models (AUC 0.99, specificity 97.2%, sensitivity 80.0%), there is no other detection benefit from RMI compared to HE4 alone or included in ROMA.

CONCLUSIONS:

The major advantage of HE4 lies in its specificity and improved detection of borderline tumors and early stage ovarian and tubal cancers. HE4 is superior to CA125 with or without RMI and ROMA indices. However, we see no benefit from combining both markers in clinical practice.

J Steroid Biochem Mol Biol. 2011 Mar 21. [Epub ahead of print]

Novel estrogen-related genes and potential biomarkers of ovarian endometriosis identified by differential expression analysis.

Vouk K, Smuc T, Guggenberger C, Ribič-Pucelj M, Sinkovec J, Husen B, Thole H, Houba P, Thaete C, Adamski J, Rižner TL.

Source

Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg, 2, 1000 Ljubljana, Slovenia.

Abstract

In the search for novel biomarkers of endometriosis, we selected 152 genes from the GeneLogic database based on results of genome-wide expression analysis of ovarian endometriosis, plus 20 genes related to estrogen metabolism and action. We then performed low-density array analysis of these 172 genes on 11 ovarian endometriosis samples and 9 control endometrium samples. Principal component analysis of the gene expression levels showed clear separation between the endometriosis and control groups. We identified 78 genes as differentially expressed. Based on Ingenuity pathway analysis, these differentially expressed genes were arranged into groups according to biological function. These analyses revealed that 32 differentially expressed genes are estrogen related, 23 of which have not been reported previously in connection with endometriosis. Functional annotation showed that 25 and 22 genes are associated with the biological terms “secreted” and “extracellular region”, respectively. Differential expression of 4 out of 5 genes related to estrogen metabolism and action (ESR1, ESR2, PGR and BGN) was also confirmed by immunohistochemistry. Our study thus reveals differential expression of several genes that have not previously been associated with endometriosis and that encode potential novel biomarkers and drug targets.

PLoS One. 2011 Mar 21;6(3):e18074.

The Role of DJ-1 in the Pathogenesis of Endometriosis.

Rai P, Shivaji S.

Source

Centre for Cellular and Molecular Biology, Hyderabad, India.

Abstract

BACKGROUND:

Endometriosis is an estrogen-dependent disease causing pelvic pain and infertility in 10% of reproductive-aged women. Despite a long history of the disease the pathogenesis of endometriosis is poorly understood. It is known that the expression of several proteins is either up or down regulated during endometriosis, but their precise role remains to be determined. DJ-1 is one such protein that is upregulated in eutopic endometrium of women having endometriosis suggesting that DJ-1 may be involved in the pathogenesis of endometriosis.

METHODOLOGY AND PRINCIPAL FINDINGS:

The role of DJ-1 in the pathogenesis of endometriosis was investigated. For this purpose the influence of DJ-1 on endometrial cell survival, attachment, proliferation, migration, and invasion either by overexpressing DJ-1 in normal endometrial cells or by knocking down DJ-1 expression in endometriotic cells using siRNA was investigated. The results indicated that DJ-1 protects endometrial cells from oxidative stress mediated apoptosis. Overexpression of DJ-1 in normal endometrial epithelial cells increases the adhesion on collagen type IV. However, no significant difference was observed incase of stromal cells. It was further demonstrated that DJ-1 regulates cell proliferation, migration, and invasion in normal endometrial and endometriotic epithelial cells whereas in the case of normal endometrial and endometriotic stromal cells, it regulates cell proliferation and invasion but not migration. Furthermore, the present study also indicated that DJ-1 regulates these cellular processes by modulating PI3K/Akt pathway by interacting and negatively regulating PTEN.

CONCLUSIONS:

Abnormally high levels of DJ-1 expression may be involved in endometriosis, possibly by stimulating endometrial cell survival, proliferation, migration, and invasion.

Arch Gynecol Obstet. 2011 Mar 20. [Epub ahead of print]

Accessory ovary in the utero-ovarian ligament: an incidental finding.

Benbara A, Tigaizin A, Carbillon L.

Source

Department of Gynecology and Obstetrics, Jean Verdier Hospital, AP-HP, Paris XIII University, Avenue du 14 Juillet, 93143, Bondy Cedex, France, amelie.benbara@jvr.aphp.fr.

Abstract

BACKGROUND:

So far, only 21 descriptions of accessory ovary have been reported since 1959. However, the true incidence of this condition is probably underestimated because the pathologic forms (ovarian tumors and endometriosis) are probably more often diagnosed and reported.

CASE:

We report the incident discovery of one right accessory ovary during a laparoscopic tubal sterilization. This accessory ovary was asymptomatic and structurally normal. It was connected serial to the right utero-ovarian ligament and left in situ. There was no other anomaly.

CONCLUSION:

Gynaecologic surgeons must be aware of this possibility when removal of the whole ovarian tissue is needed.

Analyst. 2011 Mar 18. [Epub ahead of print]

Fourier-transform infrared spectroscopy discriminates a spectral signature of endometriosis independent of inter-individual variation.

Cheung KT, Trevisan J, Kelly JG, Ashton KM, Stringfellow HF, Taylor SE, Singh MN, Martin-Hirsch PL, Martin FL.

Source

Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster, LA1 4YQ, UK. f.martin@lancaster.ac.uk.

Abstract

Endometriosis is the growth of endometrial tissue outside of the uterine cavity. Its aetiology remains obscure, and it is difficult to diagnose ranging from asymptomatic to debilitating disease. Mid-infrared (IR) spectroscopy has become recognised as a potential clinical diagnostic tool. Biomolecules absorb mid-IR (4000 cm(-1) to 400 cm(-1)) and from this, a biochemical-cell fingerprint in the form of an absorbance spectrum can be derived. We set out to determine if IR spectroscopy could be used to identify underlying biochemical differences between endometrial tissues growing outside of the uterus (ectopic) from endometrial tissue of the uterus (eutopic). For comparative purposes, endometrial tissues from endometriosis-free women were also obtained (benign eutopic). Attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy or transmission FTIR microspectroscopy was employed for spectral acquisition. Principal component analysis (PCA)-linear discriminant analysis (LDA) was used for chemometric analysis. A clear segregation was exhibited between the three categories independent of inter-individual confounding differences. Importantly, there was a marked difference between eutopic endometrial tissue from patients with or without endometriosis. This indicates that IR spectroscopy coupled with multivariate analysis (e.g., PCA-LDA) may provide a non-invasive diagnostic tool for endometriosis. By analysing the underlying biochemistry of these endometrial tissues, this approach may facilitate a better understanding of this pathology.

J Minim Invasive Gynecol. 2011 Mar 18. [Epub ahead of print]

Is Pouch of Douglas Obliteration a Marker of Bowel Endometriosis?

Khong SY, Bignardi T, Luscombe G, Lam A.

Source

Centre for Advanced Reproductive Endosurgery (Drs. Khong, Bignardi, and Lam), the Department of Obstetrics and Gynaecology, DMSD San Paolo, University of Milano, Italy (Dr. Bignardi), the Department of Obstetrics and Gynaecology, University of Sydney, Australia (Drs. Lam and Luscombe), and the Department of Obstetrics and Gynaecology, University of Malaya, Malaysia (Dr. Khong).

Abstract

STUDY OBJECTIVE:

To estimate the clinical significance of pouch of Douglas (POD) obliteration in women undergoing laparoscopic excision of endometriosis.

DESIGN:

Prospective study (Canadian Task Force Classification II-2).

SETTING:

University-affiliated tertiary referral center for endometriosis.

PATIENTS:

A total of 454 consecutive women who underwent laparoscopic surgery for treatment of pelvic pain or infertility-associated endometriosis between October 2004 and September 2008.

INTERVENTIONS:

Demographic, historical, and final surgical data were compared between women with and without POD obliteration at laparoscopy. Logistic regression analyses were performed to investigate the predictive value of POD obliteration at laparoscopy with regard to bowel endometriosis.

MEASUREMENTS AND MAIN RESULTS:

One hundred consecutive women with POD obliteration at laparoscopy were included. 58% (95% confidence interval [CI] 0.48-0.67, n = 58/100) of the women with POD obliteration required bowel surgery compared with 20% (95% CI 0.16-0.25, 72/354) of women without POD obliteration (p <.001). Of the POD obliteration group, 66% (95% CI 0.53-0.76) required bowel shaving, 12% (0.06-0.23) full segmental rectal resection, 9% (0.04-0.19) wedge rectal resection, 5% (0.02-0.14) full segmental rectosigmoid resection and 9% (0.04-0.19) a combination of the above. Bowel endometriosis was histologically confirmed in all women.

CONCLUSION:

POD obliteration at laparoscopy carries a high risk of bowel endometriosis and bowel surgery. This risk is three times higher than those without POD obliteration. Women with POD obliteration should be managed in tertiary referral centers for the treatment of endometriosis where colorectal input is available.

Surg Endosc. 2011 Mar 18. [Epub ahead of print]

Comparison between standard and reverse laparoscopic techniques for rectovaginal endometriosis.

Kondo W, Bourdel N, Jardon K, Tamburro S, Cavoli D, Matsuzaki S, Botchorishvili R, Rabischong B, Pouly JL, Mage G, Canis M.

Source

Department of Gynecologic Surgery, CHU Estaing, Clermont-Ferrand, France, williamkondo@yahoo.com.

Abstract

BACKGROUND:

This study was designed to compare the surgical outcomes of standard and reverse laparoscopic techniques for the treatment of rectovaginal endometriosis.

METHODS:

A retrospective study was conducted in a teaching and research hospital (tertiary center), which included 75 women subjected to laparoscopic treatment of rectovaginal endometriosis that required both vaginal resection and rectal surgery. Standard and reverse laparoscopic techniques were compared in 35 and 40 women, respectively. Student’s t test, Mann-Whitney test, and Fisher’s exact test were performed to compare groups when needed; p < 0.05 was considered statistically significant.

RESULTS:

There was no statistically significant difference in operating time, blood loss, conversion rate, major intraoperative complications, length of hospital stay, and minor postoperative complications between the two techniques. The rate of major postoperative complications for the standard technique was 22.9%, whereas only 5% for the reverse technique (p = 0.02). The rate of postoperative rectovaginal fistula was the same for both techniques.

CONCLUSIONS:

Major postoperative complications were reduced by using the reverse technique.

Annu Rev Physiol. 2011 Mar 17;73:163-82.

Endometriosis: the role of neuroangiogenesis.

Asante A, Taylor RN.

Source

Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Abstract

Endometriosis is a common cause of pelvic pain and infertility, affecting ∼10% of reproductive-age women. Annual costs for medical and surgical care in the United States exceed $20 billion. The disorder is characterized by implants of endometrial tissue outside the uterine cavity. Endometriotic lesions induce a state of chronic peritoneal inflammation, accompanied by elevated prostaglandin, cytokine, and growth factor concentrations. The current therapy is surgical ablation of ectopic implants and hormones that block the hypothalamic-pituitary-ovarian axis, but these approaches are expensive, carry perioperative risks, or have unpleasant side effects of hypoestrogenism. Recent evidence indicates that ectopic endometriotic implants recruit their own unique neural and vascular supplies through neuroangiogenesis. It is believed that these nascent nerve fibers in endometriosis implants influence dorsal root neurons within the central nervous system, increasing pain perception in patients. We consider the mechanisms and therapeutic implications of neuroangiogenesis in these lesions and propose potential treatments for the control or elimination of endometriosis-associated pain.

Fertil Steril. 2011 Mar 15;95(4):1421-7. Epub 2011 Feb 12.

Deoxyribonucleic acid methyltransferases and methyl-CpG-binding domain proteins in human endometrium and endometriosis.

van Kaam KJ, Delvoux B, Romano A, D’Hooghe T, Dunselman GA, Groothuis PG.

Source

GROW, School for Oncology and Developmental Biology, University of Maastricht, Maastricht, the Netherlands. kimvankaam@yahoo.com

Abstract

OBJECTIVE:

To determine [1] expression levels of both DNA methyltransferases (DNMTs) and methyl-CpG-binding domain proteins (MBDs) in human endometrium throughout the menstrual cycle and in eutopic and ectopic endometrium of patients with endometriosis and [2] hormone responsiveness of DNMT and MBD expression in explant cultures of proliferative phase endometrium.

DESIGN:

In vitro study.

SETTING:

Academic medical center.

PATIENT(S):

Premenopausal women with and without endometriosis.

INTERVENTION(S):

Explant cultures of proliferative phase endometrium were treated with vehicle, 17β-E(2), or a combination of E(2) and P (E(2) + P) for 24 hours.

MAIN OUTCOME MEASURE(S):

Expression levels of DNMT1, DNMT2, and DNMT3B and MBD1, MBD2, and MeCP2 with use of real-time quantitative polymerase chain reaction.

RESULT(S):

Expression levels of DNMT1 and MBD2 were significantly higher in secretory-phase endometrium compared with proliferative endometrium and menstrual endometrium. In explant cultures, treatment with E(2) + P resulted in significant up-regulation of DNMT1 and MBD2. Expression levels of several DNMTs and MBDs were significantly lower in endometriotic lesions compared with eutopic endometrium of women with endometriosis and disease-free controls.

CONCLUSION(S):

These findings suggest a role for DNMTs and MBDs in the growth and differentiation of the human endometrium and support the notion that endometriosis may be an epigenetic disease.

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