Hum Reprod. 2012 Oct;27(10):2955-65. doi: 10.1093/humrep/des152. Epub 2012 Aug 1.

Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis.

Vouk K1Hevir NRibić-Pucelj MHaarpaintner GScherb HOsredkar JMöller GPrehn CRižner TLAdamski J.

 

Abstract

BACKGROUND:

Current non-invasive diagnostic methods for endometriosis lack sensitivity and specificity. In search for new diagnostic biomarkers for ovarian endometriosis, we used a hypothesis-generating targeted metabolomics approach.

METHODS:

In a case-control study, we collected plasma of study participants and analysed their metabolic profiles. We selected a group of 40 patients with ovarian endometriosis who underwent laparoscopic surgery and a control group of 52 healthy women who underwent sterilization at the University Clinical Centre Ljubljana, Slovenia. Over 140 targeted analytes included glycerophospholipids, sphingolipids and acylcarnitines. The analytes were quantified by electrospray ionization tandem mass spectrometry. For assessing the strength of association between the metabolite or metabolite ratios and the disease, we used crude and adjusted odds ratios. A stepwise logistic regression procedure was used for selecting the best combination of biomarkers.

RESULTS:

Eight lipid metabolites were identified as endometriosis-associated biomarkers due to elevated levels in patients compared with controls. A model containing hydroxysphingomyelin SMOH C16:1 and the ratio between phosphatidylcholine PCaa C36:2 to ether-phospholipid PCae C34:2, adjusted for the effect of age and the BMI, resulted in a sensitivity of 90.0%, a specificity of 84.3% and a ratio of the positive likelihood ratio to the negative likelihood ratio of 48.3.

CONCLUSIONS:

Our results suggest that endometriosis is associated with elevated levels of sphingomyelins and phosphatidylcholines, which might contribute to the suppression of apoptosis and affect lipid-associated signalling pathways. Our findings suggest novel potential routes for therapy by specifically blocking highly up-regulated isoforms of phosphpolipase A2 and lysophosphatidylcholine acyltransferase 4.

 

 

 

J Obstet Gynecol Neonatal Nurs. 2012 Sep-Oct;41(5):692-702. doi: 10.1111/j.1552-6909.2012.01405.x. Epub 2012 Aug 3. Review.

Sexual adjustment counseling for women with chronic pelvic pain.

Howard HS.

 

Abstract

Sexual concerns are common in women with chronic pelvic pain and often remain unresolved when pain improves. Therefore, to restore pelvic function, treatment should address sexuality in addition to pain. In this article, I describe sexual challenges experienced by women with chronic pelvic pain, introduce a modified sexuality counseling model, and suggest sexuality resources and training for gynecologic nurses and other health care providers who are ideally positioned to offer sexuality counseling to this population.

 

 

 

J Minim Invasive Gynecol. 2012 Sep-Oct;19(5):572-4. doi: 10.1016/j.jmig.2012.06.005. Epub 2012 Aug 3. Review.

Granulosa cells in the uterosacral ligament: case report and review of the literature.

Pun JJ1Vilos GAEttler HCMarks JVilos AGAbu-Rafea B.

 

Abstract

Granulosa cells are components of the sex cord-stromal cells in the ovary responsible for steroidogenesis. Uncommonly, extraovarian granulosa cells have been reported to be associated with malignant processes of the ovary. We report a unique case of benign granulosa cells, found during routine laparoscopic evaluation, in the uterosacral ligaments in a 20-year-old patient with chronic pelvic pain and infertility. Possible mechanisms include implantation of released granulosa cells from a normal ovary or arising from a focus of müllerianosis. Of note, a focus of endosalpingiosis and endometriosis was also identified within the specimen.

 

 

 

Cell Tissue Res. 2012 Sep;349(3):631-3. doi: 10.1007/s00441-012-1480-y.

Cell biology solves mysteries of reproduction.

Sutovsky P.

 

Abstract

Reproduction and fertility have been objects of keen inquiry since the dawn of humanity. Medieval anatomists provided the first accurate depictions of the female reproductive system, and early microscopists were fascinated by the magnified sight of sperm cells. Initial successes were achieved in the in vitro fertilization of frogs and the artificial insemination of dogs. Gamete and embryo research was in the cradle of modern cell biology, providing the first evidence of the multi-cellular composition of living beings and pointing out the importance of chromosomes for heredity. In the 20th century, reproductive research paved the way for the study of the cytoskeleton, cell signaling, and the cell cycle. In the last three decades, the advent of reproductive cell biology has brought us human in vitro fertilization, animal cloning, and human and animal embryonic stem cells. It has contributed to the development of transgenesis, proteomics, genomics, and epigenetics. This Special Issue represents a sample of the various areas of reproductive biology, with emphasis on molecular and cell biological aspects. Advances in spermatology, ovarian function, fertilization, and maternal-fetal interactions are discussed within the framework of fertility and diseases such as endometriosis and diabetes.

 

 

 

Reprod Sci. 2012 Dec;19(12):1365-72. doi: 10.1177/1933719112450340. Epub 2012 Aug 7.

Expression profile of extracellular matrix and adhesion molecules in the development of endometriosis in a mouse model.

Umezawa M1Saito YTanaka-Hattori NTakeda KIhara TSugamata M.

 

Abstract

Ectopic endometrial tissue induces various reactions in surrounding tissues, such as the surface of the ovary and peritoneal cavity, leading to endometriosis. The aim of this study is to investigate the expression profile of extracellular matrix (ECM) and adhesion molecules in the early steps of development of experimental mouse endometriosis, specifically in peritoneum adjacent to endometrium transplants attached via autotransplantation. The endometriosis model was induced by autotransplantation of endometrium to peritoneal tissue. Peritoneal tissues adjacent to the transplant were obtained at 1, 4, and 7 days posttransplantation. The results showed that messenger RNA expression levels of most of the integrins, collagens, and other ECM reached a peak at 7 days posttransplantation. Uniquely, Lamc2 was significantly increased to its maximum level within 24 hours posttransplantation and may be strongly associated with initiation of the development of endometriosis. These data will be helpful in further investigations of the treatment of endometriosis.

 

 

 

Eur J Gynaecol Oncol. 2012;33(3):324-5. Review.

Endometrioid ovarian cancer arising from an endometriotic cyst in a young patient.

Zygouris D1Leontara VMakris GMChrelias CTrakakis EChristodoulaki ChPanagopoulos P.

 

Abstract

OBJECTIVE:

To present a case of a young woman with ovarian endometrioid adenocarcinoma arising from an endometriotic cyst and review of the literature.

CASE REPORT:

A 33-year-old woman, gravid 2, para 2 was admitted to our department with a 5 cm adnexal mass. Diagnostic laparoscopy was performed and pathological examination demonstrated an endometriotic cyst with an area of an ovarian endometrioid adenocarcinoma well differentiated, with no capsular invasion. One month after the operation the patient underwent MRI which revealed a 6 cm mass in the Douglas pouch. The multidisciplinary oncology council decided on exploratory laparotomy, which revealed no pathology. After that the multidisciplinary oncology council decided on adjuvant chemotherapy and the patient received four cycles of carboplatin/taxol.

CONCLUSION:

It should always be considered that even when there are no risk factors for malignancy occurrence, a high index of suspicion is necessary and will help to prevent delay in the diagnosis of this rare neoplasm.

 

 

 

Hinyokika Kiyo. 2012 Jun;58(6):287-90. Japanese.

A case of vesical endometriosis that worsened during the early pregnancy period.

[Article in Japanese]

Aoki S1Shimada MInoue KNagata MSaito KOgawa YMatsubara EMaeda TSugahara MHayashi KMatsumoto Y.

 

Abstract

We report a case of vesical endometriosis that worsened during the early pregnancy period. A 37-year old woman had been under treatment for endometriosis (including vesical endometriosis) by a gynecologist during the past 10 years. She was treated for sterility 1 year ago, and became pregnant through in vitro fertilization. In her 8th gestational week, she complained of gross hematuria at our hospital. Cystoscopic findings revealed some tumors that appeared worse than the last findings two years ago. In order to deny malignancy, transurethral resection of the bladder tumor was performed in her 12th gestational week. The pathologic diagnosis was endometriosis. She was able to stay pregnant, and delivered a girl. After delivery, cystoscopic findings revealed reduction of tumors. In most cases pregnancy cures endometriosis ; however, in this case symptoms became worse during the early stage of pregnancy. The reason for this contrary event is discussed.

 

 

 

Dis Colon Rectum. 2012 Sep;55(9):925-31. doi: 10.1097/DCR.0b013e31825f3092.

Management of deeply infiltrating endometriosis involving the rectum.

Koh CE1Juszczyk KCooper MJSolomon MJ.

 

Abstract

BACKGROUND:

Rectal endometriosis can cause debilitating symptoms. Rectal resection in this setting has been shown to improve symptoms; however, there remain some reservations about this intervention because of the risk of complications such as anastomotic leak and rectovaginal fistula.

OBJECTIVE:

The aim of this study is to review our experience with rectal resection in patients with rectal endometriosis.

DATA SOURCES:

Hospital records and prospectively maintained electronic databases of an endogynecologist and colorectal surgeon were reviewed.

STUDY SELECTION:

This is a retrospective study of consecutive patients who underwent rectal resection for endometriosis from 2001 to 2010.

INTERVENTIONS:

All patients underwent either disc or segmental resection of the rectum.

MAIN OUTCOME MEASURES:

Outcomes of interest were operative complications and recurrence requiring surgical reintervention.

RESULTS:

Ninety-one patients underwent 92 resections for endometriosis. Sixty-five (71%) were disc resections, 25 (27%) were segmental resections, and 1 patient underwent both disc and segmental resections. Eighty-one (88%) procedures were completed laparoscopically. Patients requiring segmental resection had more extensive disease, and this was associated with open conversion (p ≤ 0.0001). Average duration of procedure was 209 minutes. Three patients (3%) required defunctioning ileostomies. Intramural endometriosis was confirmed in 96.7% of specimens. Complications occurred in 13 patients (15%); 4 were minor. Three patients had small pelvic collections treated with antibiotics, 5 patients required transfusion for bleeding (3 intraoperative, 2 anastomotic bleeds that settled conservatively), and 1 patient sustained ureteric injury that was reimplanted with no sequelae. None had anastomotic leak or rectovaginal fistula. Ten patients (11%) required reintervention for recurrent symptoms. Of these, 8 (8.8%) patients were found to have recurrent endometriosis. No correlation could be found between involved margins on pathology and need for redo surgery.

LIMITATIONS:

: This study is limited by its retrospective nature.

CONCLUSIONS:

Laparoscopic rectal resection for deeply infiltrative endometriosis is feasible and safe, and it provides durable symptom control with acceptable recurrence rates.

 

 

 

Reprod Sci. 2012 Oct;19(10):1018-29. doi: 10.1177/1933719112446080. Epub 2012 Aug 8. Review.

2-methoxyestradiol in the pathophysiology of endometriosis: focus on angiogenesis and therapeutic potential.

Machado-Linde F1Pelegrin PSanchez-Ferrer MLLeon JCascales PParrilla JJ.

 

Abstract

Endometriosis is a common condition among women of childbearing potential in which ectopic endometrial tissue is found outside the uterine cavity. Neoangiogenesis plays a major role in the development of endometriotic implants. Some evidence suggests that a disorder in the balance of proangiogenic and antiangiogenic factors that favors the former is induced by local hypoxia and is mediated by the hypoxia-inducible factor-vascular endothelium growth factor pathway could partially explain the development of this condition in some women. 2-methoxyestradiol is a biologically active metabolite of estradiol having antiangiogenic action. Changes in estradiol homeostasis have been locally observed in endometriosis. In this review, we summarize current knowledge of endometriosis pathophysiology, in particular, the balance between local 2-methoxyestradiol production and angiogenesis, which could promote the development of endometriotic lesions. 2-Methoxyestradiol emerges as a promising new candidate for the treatment of endometriosis.

 

 

 

 

Reprod Sci. 2013 Mar;20(3):285-98. doi: 10.1177/1933719112452940. Epub 2012 Aug 8.

Slit2 overexpression results in increased microvessel density and lesion size in mice with induced endometriosis.

Guo SW1Zheng YLu YLiu XGeng JG.

 

Abstract

We recently reported that Slit/Roundabout (ROBO) 1 pathway may be a constituent biomarker for recurrence of endometriosis, likely through promoting angiogenesis. In this study, we sought to determine as whether Slit2 overexpression can facilitate angiogenesis, increase lesion size, and induce hyperalgesia in mice with induced endometriosis. We used 30 Slit2 transgenic (S) and 29 wild-type (W) mice and cross-transplanted endometrial fragments from S to W (group SW) and vice versa (group WS), and also within the S and W (groups SS and WW, respectively), into the peritoneal cavity, inducing endometriosis. We also performed a sham surgery within both S and W mice (groups Sm and Wm, respectively). The size of the ectopic implants, microvessel density (MVD) and immunoreactivity to ROBO1, and vascular endothelial cell growth factor (VEGF) in ectopic and eutopic endometrium, along with hotplate and tail-flick tests in all mice, were then evaluated. We found that the induction of endometriosis resulted in generalized hyperalgesia, which was unaffected by Slit2 overexpression. Slit2 overexpression did increase the lesion size significantly and correlated positively with the MVD in ectopic and eutopic endometrium. Slit2 expression levels appear to correlate with the MVD, but not with VEGF immunoreactivity, in ectopic endometrium. Consequently, we conclude that Slit2 may play an important role in angiogenesis in endometriosis. The increased angiogenesis, as measured by MVD, but not VEGF immunoreactivity, likely resulted in increased lesion size in induced endometriosis. Thus, SLIT2/ROBO1 pathway may be a potential therapeutic target for treating endometriosis.

 

 

 

J Steroid Biochem Mol Biol. 2012 Nov;132(3-5):303-10. doi: 10.1016/j.jsbmb.2012.07.004. Epub 2012 Jul 31.

Effects of progestins on local estradiol biosynthesis and action in the Z-12 endometriotic epithelial cell line.

Beranič N1Rižner TL.

 

Abstract

Endometriosis is a common estrogen-dependent gynecological disease. In patients with endometriosisestradiol can be synthesized locally in the endometriotic lesions from inactive precursors of adrenal or ovarian origin, via the aromatase pathway. These increased estradiol levels stimulate proliferation of endometriotic tissue. The progestins have been used in the therapy of endometriosis for more than 40 years but their pharmacological action is still not understood in detail. In the present study we therefore aimed to evaluate the effects of three progestins most commonly used in the therapy of endometriosis; medroxyprogesterone acetate, dydrogesterone and dienogest on expression of all genes encoding enzymes of the aromatase pathway and estrogen receptors in the Z-12 model epithelial cell line of peritoneal endometriosis, by qPCR and Western blotting. Our results show that application of medroxyprogestrone acetate, dydrogesterone and dienogest significantly decreases HSD17B1 and CYP19A1 expression and significantly increases HSD17B2 expression. Dydrogesterone and dienogest also significantly suppress ESR1 and ESR2 transcription, whereas medroxyprogestrone acetate and dydrogesterone significantly reduce mRNA levels of GPER. Our results thus suggest that in peritoneal endometriosis the beneficial effects of these progestins can be explained by lower HSD17B1 and higher HSD17B2 mRNA and protein levels, which lead to reduced local E2 biosynthesis. Although progestins significantly decrease CYP19A1 mRNA levels, the protein itself was not detectable by Western blotting. As progestins down-regulate expression of ESR1, ESR2 and GPER, they might also prevent E2-mediated proliferation.

 

 

 

Reprod Sci. 2013 Jan;20(1):85-102. doi: 10.1177/1933719112451147. Epub 2012 Aug 9.

Tissue remodeling and nonendometrium-like menstrual cycling are hallmarks of peritoneal endometriosis lesions.

Sohler F1Sommer AWachter DLAgaimy AFischer OMRenner SPBurghaus SFasching PABeckmann MWFuhrmann UStrick RStrissel PL.

 

Abstract

We identified differentially expressed genes comparing peritoneal endometriosis lesions (n = 18), eutopic endometrium (n = 17), and peritoneum (n = 22) from the same patients with complete menstrual cycles using microarrays (54 675 probe sets) and immunohistochemistry. Peritoneal lesions and peritoneum demonstrated 3901 and 4973 significantly differentially expressed genes compared to eutopic endometrium, respectively. Peritoneal lesions significantly revealed no correlation with a specific menstrual cycle phase by gene expression and histopathology, exhibited low expressed proliferation genes, and constant levels of steroid hormone receptor genes. Tissue remodeling genes in cytoskeleton, smooth muscle contraction, cellular adhesion, tight junctions, and O-glycan biosynthesis were the most significant to lesions, including desmin and smooth muscle myosin heavy chain 11. Protein expression and location of desmin, alpha-actin, and h-caldesmon in peritoneal lesions discriminated between smooth muscle hyperplasia and metaplasia. Peritoneal lesions demonstrate no menstrual cycle phasing but constant steroid hormone receptor expression where a slow but steady growth is linked with tissue remodeling. Our study contributes to the molecular pathology of peritoneal endometriosis and will help to identify clinical targets for treatment and management.

 

 

 

Ginekol Pol. 2012 Jun;83(6):454-7. Review. Polish.

Ovarian cancer–modern approach to its origin and histogenesis.

Nowak-Markwitz E1Spaczyński M.

 

 

Abstract

Ovarian cancers (OC) belong to a heterogeneous group of pathologies and are traditionally classified with regard to histological type and degree of differentiation. OC was hypothesized to originate from ovarian surface epithelium (OSE) and inclusion cysts epithelium (IC). Unfortunately this theory was never supported by any clinical or molecular evidence linking carcinogenesis with OSE and was refuted. OC subtypes demonstrate morphologic features that resemble Müllerian duct-derived epithelia of the genital tract. Investigations of the HOX gene family Müllerian epithelial differentiation markers, confirmed the HOX genes expression in many subtypes of OC but not in OSE. The first step towards connecting OC origin with other than OSE genital tract structures were epidemiological observations indicating a minor OC risk after tubal ligation in women with the BRCA mutation. The first in situ carcinoma was found in the Fallopian tube fimbriae. Further research confirmed the same mechanism in sporadic OC. Endometriosis and endometrium cells may be a highly probable place of endometrioid OC initiation. Mucinous types share common futures with gastrointestinal tract cancers and there one needs to search for their precursors. Clear cell carcinoma may arise from glandular epithelium of endocervix or from endometrioid foci. The new classification of OC was proposed in 2004, suggesting to divide all OC into two types: I and II. Type II includes serous and endometrioid G3 subtypes, carcinosarcomas and undifferentiated OC. They are responsible for 75% of OC morbidity identified usually in FIGO stages Ill or IV, have poor prognosis and relapse early The remaining hystiotypes, with better prognosis and earlier FIGO stages at time of diagnosis, were classified as type I. Serous and endometrioid poorly differentiated ovarian cancers demonstrate mutation in TP53 gene (type II) and highly differentiated ones, generally in BRAS and KRAS genes (type I). The differences in molecular pathways also confirm different patterns of carcinogenesis of both OC types. Modern approach to OC histogenesis and origin emphasizes the necessity to verify OC screening, detection and treatment methods.

 

 

 

 

J Cutan Pathol. 2012 Nov;39(11):1035-41. doi: 10.1111/j.1600-0560.2012.01982.x. Epub 2012 Aug 11. Review.

Clear cell adenocarcinoma arising from endometriosis in abdominal wall cesarean section scar: a case report and review of the literature.

Shalin SC1Haws ALCarter DGZarrin-Khameh N.

 

Abstract          

Malignancy arising in association with endometriosis is a rare but well-documented phenomenon that was first described in the literature as early as 1925. Cutaneous endometriosis with subsequent malignant transformation is even more uncommon, and high clinical suspicion is required for diagnosis. The clinical differential diagnosis of these lesions includes a wide variety of entities, ranging from benign cysts to malignancies such as melanoma. We report a case of clear cell adenocarcinoma arising from endometriosis in a cesarean section scar in a 47-year-old woman, and we complete a review of the literature regarding this unusual entity.

 

 

 

Zhonghua Yi Xue Za Zhi. 2012 May 22;92(19):1352-6. Chinese

Effects of activating and inhibiting Wnt/β-catenin signaling pathway on murine model of eutopic endometrium and endometriosis.

Liang JY1Li CDZhang WY.

 

Abstract

OBJECTIVE:

To employ the classical Wnt/β-catenin signaling pathway interference to explore the effects on the functional changes of eutopic endometrium stromal cells and the differences between endometriosis in a murine model.

METHODS:

Two out of three mouse groups received an injection of either Wnt/β-catenin signaling pathway activator or blocker. Later the endometrial tissue samples were obtained to develop endometrial stromal cell cultures for the detection of cell invasion ability via Boyden chamber invasion assay and Western blot (WB). Then the methods of WB and Immunohistochemical staining (IHC) were used to examine the factors of eutopic endometrium. And an endometriosis model was established to investigate the factors of signaling pathway via quantitative polymerase chain reaction (QPCR) and IHC.

RESULTS:

According to WB test, the level of β-catenin, GSK-3β and APC in the activation group were significantly higher than in the inhibition group (P < 0.01). In Boyden chamber invasion assay, the number of cells on membranes in the trial group was significantly higher than the control group [(113 ± 12) vs (64 ± 13)]. The expressions of VEGF and MMP-9 in the endometrial stromal cells culture from Boyden chamber assay analyzed via WB were ranked from highest to lowest respectively as activation group (vs control group was 35.6% and 27.4% higher), control group and inhibition group (vs control group was 12.3% and 30.4% lower). Furthermore, the endometrial E-cadherin and VEGF examined via IHC respectively showed a positive expression in inhibitor group and strong positive expression in activation group. QPCR showed the level of Wnt3, Wnt7, GSK3β, Lef and E-cadherin in the activation group was higher than those in the inhibition group (P < 0.05).

CONCLUSION:

The intervention of WNT signaling pathway in vivo cause the changes of eutopic endometrial invasion and adhesion function, and further affect the development of endometriosis. Wnt/β-catenin signaling pathway may promote the eutopic endometrial cell proliferation and improve the ability of eutopic endometrial implantation, invasion, metastasis and angiogenesis.

 

 

 

 

Zhonghua Fu Chan Ke Za Zhi. 2012 May;47(5):324-7. Chinese.

Study on the relationship between altered expression of annexin A4 and endometrial receptivity during the implantation window in infertile patients with endometriosis.

Jiang YL1Li BXing FQWang FFeng JH.

 

Abstract

OBJECTIVE:

To identify the differential expressed proteins, and to investigate the relationship between altered expression of annexin A4 during window of implantation [WOI (at day-6 after ovulatory day)] in infertile patients with endometriosis and endometrial receptivity.

METHODS:

Two-dimensional fluorescence differential in-gel electrophoresis (2D-DIGE) and matrix-assist laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS) were used to detect protein expression in endometrial WOI in 10 infertile cases with endometriosis as endometriosis group and 10 infertile cases with tubal factors as control group. The semi-quantitative validation of annexin A4 in the eutopic endometrial tissue during WOI was analyzed by western blot.

RESULTS:

By comparing protein profiles, there were 7 meaningful differential proteins during WOI in infertile patients with endometriosis. One protein with an isoelectric point of 5.84 and relative molecular weight of 36 100 were down regulated 348% in samples of endometriosis group. It was identified as annexin A4 by mass spectrometry. By western blot, relative intensity of annexin A4 in endometriosis group was 7.2 ± 0.9, which was lower than 17.8 ± 2.6 in control group significantly (t = 7.654, P = 0.002).

CONCLUSION:

Lower expression of annexin A4 during WOI in infertile patients with endometriosis might be associated with the decrease of endometrial receptivity.

 

 

 

 

Zhonghua Fu Chan Ke Za Zhi. 2012 May;47(5):328-32. Chinese.

Association of the tumor necrosis factor-alpha -1031T/C and its combination with interleukin-6 -634C/G gene polymorphisms with susceptibility to endometriosis.

Mao T1Zong LLWang YFZeng JFu YGZhao XRao XQHuang YXXu ZMZhu XN.

 

Abstract

OBJECTIVE:

To investigate the association of tumor necrosis factor-alpha (TNF-α) gene promoter region -1031T/C and its combination with interleukin-6 (IL-6) gene promoter region -634C/G single nucleotide polymorphisms (SNP) with the genetic susceptibility to endometriosis.

METHODS:

Total of 432 endometriosis patients and 499 non-endometriosis women who had received an operation due to tubal ligation, tubal recanalization, laparoscopic hydrotubation, ovarian simple cyst and teratoma were collected and separated into endometriosis group and control group, that all cases were confirmed by operation and pathology. A case-control study was performed in endometriosis and control group to evaluate the association of these SNP with the susceptibility to endometriosis by using a fluorescent quantitative PCR-based high resolution melting (HRM) method.

RESULTS:

(1) TNF-α -1031T/C genotype:the T and C of TNF-α -1031T/C allele frequencies in the endometriosis group and control group were 79.2% (684/864), 20.8% (180/864) and 81.8% (816/998), 18.2% (182/998), respectively. The TT, TC and CC of TNF-α -1031T/C genotype frequencies in the two groups were 63.7% (275/432), 31.0% (134/432), 5.3% (23/432) and 66.5% (332/499), 30.5% (152/499), 3.0% (15/499), respectively. There were no statistical significances in the TNF-α -1031T/C alleles and genotypes distributions between the two groups (P = 0.158, P = 0.186). (2) TNF-α -1031T/C and IL-6 -634C/G conjoint genotypes: to research on the TNF-α -1031T/C and IL-6 -634C/G genotypes for conjoint analysis, the TT+CC, TC+CC, CC+CC, TT+CG, TC+CG, CC+CG, TT+GG, TC+GG and CC+GG combination genotype frequencies in the two groups were 39.4% (170/432), 19.4% (84/432), 4.6% (20/432), 20.6% (89/432), 8.8% (38/432), 0.9% (4/432), 3.5% (15/432), 2.3% (10/432), 0.5% (2/432) and 36.7% (183/499), 17.4% (87/499), 1.4% (7/499), 26.1% (130/499), 10.4% (52/499), 1.2% (6/499), 3.8% (19/499), 2.6% (13/499), 0.4% (2/499), respectively. There were no statistical significances in the combination genotypes distributions between the two groups (P = 0.107). As compared with carriers of TT+CC combination genotype, the endometriosis risk of carriers of CC+CC combination genotype enhanced 3.076 times (95%CI: 1.268 – 7.457, P = 0.009), and the endometriosis risk of carriers of other combination genotypes were no statistical significances (all P > 0.05).

CONCLUSIONS:

The study demonstrates that there are no significant association between the SNP of TNF-α -1031T/C and genetic susceptibility to endometriosis. However the results indicate that there are significant association between genetic susceptibility to endometriosis and the combination polymorphisms of TNF-α -1031T/C and IL-6 -634C/G.

 

 

 

Zhonghua Fu Chan Ke Za Zhi. 2012 May;47(5):333-6. Chinese.

Expression of transient receptor potentials of vanilloid subtype 1 and pain in endometriosis.

Song N1Leng JHLang JH

 

 

Abstract

OBJECTIVE:

To investigate the expression of transient receptor potential vanilloid subtype 1 (TRPV1) in uterosacral ligament and its correlation with pain in endometriosis.

METHODS:

Total of 54 patients undergoing endometriotic lesions excision in uteroscaral ligament by laparoscopy due to pelvic pain were enrolled in this study. According to visual analogue scale (VAS) scores, 27 patients with VAS 5-10 were in group A and 27 patients with VAS 0-4 were in group B. In the mean time, 20 patients with dysmenorrhea without endometriosis (VAS: 0-4) were matched as group C. Specimens (including the sacro-ligaments of 20 women without endometriosis) were immunostained with specific antibodies of TRPV1. Western blot and real time PCR were performed to detect TRPV1 expression in endometriosis lesions and control group.

RESULTS:

(1) Immunohistochemnistry: the positive area of TRPV1 was found in endometriotic lesions in uterosacral ligament in group A, B and tissue of uterosacral ligament group C. The semi-qualitification of TRPV1 expression were 3 in group A, 1 in group B and 1 in group C by immunohistochemistry staining. There was significantly different expression between group B and group A (P = 0.005) or group C (P = 0.027). (2) mRNA expression:the expression of TRPV1 was 1.84 in group A, 0.80 in group B, 0.24 in group C, respectively. With higher VAS scores, the expression of TRPV1 exhibited increasing trends. The expression of TRPV1 mRNA was higher in group A than that in group B (P = 0.022). There was statistically different expression between group B and group C (P = 0.031). (3) Western blot: the expression of TRPV1 protein was 0.63 in group A, 0.19 in group B, 0.02 in group C. There was significant differences between group A and group B (P = 0.022), and between group B and group C (P < 0.01).

CONCLUSION:

The expression of TRPV1 was correlated with the degree of pain in patient with endometriosis.

 

 

 

Can Assoc Radiol J. 2014 Feb;65(1):9-18. doi: 10.1016/j.carj.2012.02.001. Epub 2012 Aug 9. Review.

The abdominal wall lumps and bumps: cross-sectional imaging spectrum.

Virmani V1Sethi V2Fasih N2Ryan J2Kielar A2

 

 

Abstract

This article focuses on the cross-sectional imaging spectrum of abnormalities that affect the abdominal wall, with emphasis on magnetic resonance imaging (MRI). Cross-sectional imaging is valuable for diagnosing and evaluating the extent of abdominal-wall masses. With the increasing use of MRI, it is often possible to reach a diagnosis or narrow the differential diagnosis, thereby guiding effective management. Neoplastic and non-neoplastic pathologies will be illustrated, and the distinctive imaging characteristics of these entities will be highlighted.

 

 

Fertil Steril. 2012 Nov;98(5):1200-8. doi: 10.1016/j.fertnstert.2012.06.056. Epub 2012 Aug 11.

The expression of estrogen receptors as well as GREB1, c-MYC, and cyclin D1, estrogen-regulated genes implicated in proliferation, is increased in peritoneal endometriosis.

Pellegrini C1Gori IAchtari CHornung DChardonnens EWunder DFiche MCanny GO.

 

 

Abstract

OBJECTIVE:

To analyze the expression of estrogen receptors α and β as well as their target genes implicated in proliferation, c-myc, cyclin D1, and GREB1, in the endometrium of women with or without endometriosis.

DESIGN:

Expression analysis in human tissue.

SETTING:

University hospitals and a clinic.

PATIENT(S):

Ninety-one premenopausal women (59 patients with endometriosis and 32 controls) undergoing laparoscopic surgery.

INTERVENTION(S):

Biopsies were obtained at time of surgery, performed during the proliferative phase of the cycle.

MAIN OUTCOME MEASURE(S):

Estrogen receptors α and β as well as c-myc, cyclin D1, and GREB1 mRNA expression levels were determined by quantitative reverse transcriptase-polymerase chain reaction. Tissue localization of these estrogen-regulated genes was analyzed by immunohistochemistry.

RESULT(S):

Estrogen receptors α and β as well as c-myc, cyclin D1, and GREB1 mRNA expression levels were increased in ectopic tissue in comparison with both normal and eutopic endometrium. Estrogen receptor mRNA levels also were upregulated in the eutopic peritoneal tissue of patients with endometriosis. Cyclin D1 and GREB1 expression was augmented in eutopic endometrium. c-myc, cyclin D1, and GREB1 proteins exhibited a nuclear localization in ectopic endometrial tissue.

CONCLUSION(S):

This constitutes the first report of increased expression of GREB1, as well as cyclin D1 and c-myc, in peritoneal endometriotic lesions, implicating these proteins in estrogen-dependent growth in this context.

 

 

 

J Low Genit Tract Dis. 2013 Apr;17(2):142-6. doi: 10.1097/LGT.0b013e318260e32f.

Comparison of dysplastic and benign endocervical polyps.

Long ME1Dwarica DSKastner TMGallenberg MMChantigian PDMarnach MLWeaver ALCasey PM.

 

 

Abstract

OBJECTIVE:

This study aimed to estimate dysplasia rate in histologically evaluated endocervical polyps and to compare histological and clinical characteristics of dysplastic (D) polyps with those displaying representative benign changes.

MATERIALS AND METHODS:

Endocervical polyps removed at Mayo Clinic from January 1994 to December 2010 were categorized as polyp without other descriptors, benign polyp variants, adenomatous or reactive atypical (AR) polyps, and D polyps. Clinical characteristics, cervical cytological result, and polyp histological result of patients in the latter 2 categories were compared.

RESULTS:

Among the 4,328 patients with endocervical polyps, 3,656 were classified as polyp without other descriptors, 628 as benign polyp variants, 34 as AR polyps, and 9 as D polyps. Dysplasia was mild in 4 polyps, moderate in 1 polyp, and severe in 4 polyps. Overall risk of dysplasia was 0.2%. Patients with D polyps were younger (mean = 40.3 vs. 49.8 years, p = .009) and more likely to have abnormal cervical cytological result before polyp removal (67% vs. 21%, p = .014) as compared with those with AR. Patients with D polyps tended to have a polyp greater than 20 mm (44% vs. 15%, p = .074) compared with those with AR polyps. Associated endometrial pathological diagnosis was limited to a prolapsed endometrial polyp in 1 patient and submucosal endometriosis in 1 patient.

CONCLUSIONS:

Patients with D polyps were younger and had a greater likelihood of abnormal cytological result before polyp removal. No polyp size threshold below which dysplasia could be excluded was identified. No primary cervical cancer, endometrial hyperplasia, or cancer was identified.

 

 

 

 

Hum Reprod. 2012 Oct;27(10):3028-35. doi: 10.1093/humrep/des291. Epub 2012 Aug 11.

Interleukin-1β stimulates the secretion of thymic stromal lymphopoietin (TSLP) from endometrioma stromal cells: possible involvement of TSLP in endometriosis.

Urata Y1Osuga YIzumi GTakamura MKoga KNagai MHarada MHirata THirota YYoshino OTaketani Y.

 

Abstract

STUDY QUESTION:

Is thymic stromal lymphopoietin (TSLP) involved in the pathophysiology of endometriosis?

SUMMARY ANSWER:

TSLP is up-regulated by interleukin (IL)-1β and may be involved in the development of endometriosis.

WHAT IS KNOWN ALREADY:

Endometriosis is a chronic inflammatory disease in which the Th2 immune response is activated and has been suggested to promote the disease. TSLP is a master cytokine that drive Th2 immune response.

STUDY DESIGN, SIZE, DURATION:

A laboratory study.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Primary cultures of endometrioma stromal cells (ESCs) were treated with IL-1β, a typical inflammatory cytokine associated with endometriosis. Gene expression of TSLP in ESCs and secretion of TSLP protein from ESCs were studied using quantitative PCR and a specific ELISA. Interferon γ (IFNγ), a typical Th1 cytokine, and IL-4, a typical Th2 cytokine, were added to the culture to evaluate their effect on the IL-1β-induced secretion of TSLP. Inhibitors of p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK and stress-activated protein kinase/Jun amino-terminal kinase (SAPK/JNK) were added to the culture to examine intracellular signals involved in IL-1β-induced TSLP secretion. The expression of TSLP in endometrioma tissue was examined by immunohistochemistry. The concentration of TSLP in the serum and peritoneal fluid (PF) of women with or without endometriosis was measured with a specific ELISA.

MAIN RESULTS AND THE ROLE OF CHANCE:

IL-1β stimulated the expression of TSLP mRNA and secretion of TSLP protein from ESCs. IL-4 enhanced the IL-1β-induced TSLP secretion from ESCs, while IFNγ reduced it. Inhibitors of p42/44 MAPK, p38 MAPK and SAPK/JNK suppressed the IL-1β-induced secretion of TSLP from ESCs. Positive immunostaining of TSLP was observed in the stroma of endometrioma tissue. TSLP concentrations in the serum and PF were both higher in women with endometriosis compared with those without endometriosis.

LIMITATIONS, REASONS FOR CAUTION:

The present study was only in vitro. The samples used for culture were endometrioma tissues, not including other types of endometriosis. Therefore, the present findings should be interpreted with caution.

WIDER IMPLICATIONS OF THE FINDINGS:

This study provided new insights in the Th2 immune response-related mechanism in endometriosis.

STUDY FUNDING:

This study is partly supported by grants from the Ministry of Health, Labour and Welfare, and the Ministry of Education, Culture, Sports, Science and Technology. The authors have no conflicts of interest to declare.

 

 

 

Gene. 2012 Oct 15;508(1):41-8. doi: 10.1016/j.gene.2012.07.049. Epub 2012 Aug 4.

Estrogen receptor-alpha gene PvuII (T/C) and XbaI (A/G) polymorphisms and endometriosis risk: a meta-analysis.

Li Y1Liu FTan SQWang YLi SW.

 

Abstract

Estrogen receptor-alpha (ER-α) polymorphisms have been hypothesized to be associated with the risk of endometriosis (EMT) development by many epidemiological studies, however, the available results were conflicting. To derive a more precise estimation of association between the ER-α PvuII (T/C) and XbaI (A/G) polymorphisms and risk of EMT, we performed a meta-analysis. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for ER-α polymorphisms and EMT were calculated in a fixed-effects model and a random-effects model when appropriate. This meta-analysis included 20 case-control studies with 1752 cases and 1742 controls for PvuII polymorphism and 15 case-control studies with 1349 cases and 1411 controls for XbaI polymorphism. For PvuII T/C polymorphism, no obvious associations were found for all genetic models when all studies were pooled into the meta-analysis. In the subgroup analyses by ethnicity, country, HWE in controls and study sample size, a significantly increased risk was observed among Caucasians (recessive model, OR=2.56, 95% CI=1.06-6.16) and among studies without the HWE (recessive model, OR=1.85, 95% CI=1.20-2.84). For XbaI A/G polymorphism, also no obvious associations were found for all genetic models. In the subgroup analyses by ethnicity, country, HWE in controls and study sample size, still no obvious associations were found. No publication bias was found in the present study. This meta-analysis suggests that ER-α gene PvuII (T/C) and XbaI (A/G) polymorphisms may not be associated with EMT risk, while the observed increase in risk of EMT may be due to small-study bias.

Copyright © 2012 Elsevier B.V. All rights reserved.

 

 

BMJ Case Rep. 2012 Aug 13;2012. pii: bcr0320125988. doi: 10.1136/bcr.03.2012.5988.

Endometriosis: a rare cause of small bowel obstruction.

Khwaja SA1Zakaria RCarneiro HAKhwaja HA.

 

Abstract

Although endometriosis is a common condition in young women, symptomatic involvement of the small bowel is rare. The authors report the case of a 44-year-old lady initially thought to have irritable bowel syndrome who presented 1 month later with acute small bowel obstruction. A CT scan showed small bowel dilatation with a transition point in the ileum, but no distinct lesion. The patient had an exploratory laparotomy where an obstructing lesion in the terminal ileum and several enlarged mesenteric lymph nodes were identified. Consequently, a right hemicolectomy was performed. Pathology specimens showed multiple endometriotic foci in the bowel with stricturing of terminal ileum and appendiceal intussusception. This likely resulted in subocclusive episodes and intestinal obstruction. This case highlights the difficulty in establishing a preoperative diagnosis of endometriosis. Small bowel endometriosis should, therefore, be considered in the differential diagnosis of women of childbearing age who present with symptoms of obstruction.

 

 

Rev Med Liege. 2012 May-Jun;67(5-6):374-80. Review. French.

Role of genetic and environmental factors in the development of endometriosis.

Ballester M1Dehan PBéliard ABrichant GNisolle M.

 

Abstract

Endometriosis is usually described as a complex multifactorial disease involving dysregulation of estrogen metabolism, inflammatory and immunological mechanisms. Recently, many authors have questioned the environmental pollution and toxins in the formation and development of endometriotic lesions. Therefore, while dioxins and PCBs have been implicated, insufficient data are available until now to confirm this theory. Endometriosis has also been considered as a genetic disease. Indeed, early familial aggregation and twin studies noted a higher risk of endometriosis among relatives. However, demonstration of a genetic component in the pathogenesis of such a multifactorial disease is quite difficult due to many limitations such as ethnic differences, involvement of environmental factors and size of needed patients cohorts. Over the last decade, the epigenetic approach (DNA methylation, histones modifications and microRNA) has allowed to consider many new perspectives. Indeed, dysregulation (hyper- or hypomethylation) of many genes has already been highlighted. This method of analysis is the subject of numerous studies in order to develop diagnostic, prognostic and therapeutic tools for this disease which is becoming a real public health problem.

 

 

 

Am J Perinatol. 2013 May;30(5):371-5. doi: 10.1055/s-0032-1324705. Epub 2012 Aug 14.

Robotic resection of adnexal masses during pregnancy.

Eichelberger KY1Cantrell LABalthazar UBoggess KAStrauss RABoggess JF.

 

Abstract

OBJECTIVE:

To characterize the safety and feasibility of robotic adnexal surgery during pregnancy, and to compare surgical and obstetric outcomes for robotic versus laparoscopic treatment of adnexal masses during pregnancy.

STUDY DESIGN:

A retrospective cohort study of all cases of robotic resection of adnexal masses in gravid patients performed at our institution between 2006 and 2009 compared with 50 consecutive historic laparoscopic controls performed between 1999 and 2007.

RESULTS:

During the study period, 19 parturients underwent planned robotic resection of adnexal masses, all of which were uncomplicated. Compared with 50 consecutive laparoscopic controls, no differences in operative time, conversion to laparotomy, intraoperative or postoperative complications, or observed obstetric outcomes were apparent. The robotic cohort had a significantly shorter length of hospital stay (p < 0.01) and estimated blood loss (p = 0.02).

CONCLUSION:

Robotic resection of adnexal masses during pregnancy appears both safe and feasible, with similar surgical outcomes when compared with a historic laparoscopic cohort.

 

Kaohsiung J Med Sci. 2012 Jul;28(7 Suppl):S17-21. doi: 10.1016/j.kjms.2012.05.005. Epub 2012 Jul 7. Review.

Plasticizer incident and its health effects in Taiwan.

Li JH1Ko YC.

 

Abstract

The May 23, 2011, plasticizer incident was one of the most serious food safety issues that ever occurred in Taiwan. Most, if not all, plasticizer-contaminated food items were due to malicious replacement of palm oil with phthalate plasticizer(s) in the cloudy-agent formulas by two upstream manufacturers. The incumbent agencies in Taiwan took necessary actions to minimize the harm caused by the incident and to ease the panic of the general public. In this paper, the incident was briefly reviewed and the situations of phthalate exposure in general public and pregnant women were assessed. Subsequently, the associations between phthalates exposure and the adverse health effects, such as shortened anogenital distance in baby boys, premature thelarche in young girls, endometriosis, adenomyosis, and leiomyoma in women, and decreased semen quality in men, were discussed. Food safety issue has become a worldwide concern and early detection of potential new toxicants in the foods is indispensable. Therefore, it is imperative to establish an international network for early warning or sentinel on food safety.

 

 

 

Reprod Sci. 2013 Jan;20(1):26-32. doi: 10.1177/1933719112452941. Epub 2012 Aug 15.

The efficacy of bevacizumab, sorafenib, and retinoic acid on rat endometriosis model.

Ozer H1Boztosun AAçmaz GAtilgan RAkkar OBKosar MI.

 

Abstract

Blood vessels are necessary for development and maintenance of the endometriosis and blood flow supplies oxygen and essential nutrient to the disease. Local angiogenesis is regulated by vascular endothelial growth factor (VEGF) and inhibitors of VEGF may be a novel therapeutic approach. We inducted endometriosis in 43 rats and they were randomly allocated into 4 groups. The rats in group I (control n = 11) were given no medication. The rats in group II (n = 11) were given bevacizumab. The rats in group III (n = 11) were given Sorafenib, and the rats in group IV (n = 10) were given retinoic acid (RA). Then groups were compared for microvessel density, VEGF, soluble tyrosine-kinase receptor, ovarian reserve, and treatment effectivity. All these medications were effective on endometriosis and we detected that volume of endometriotic implants were significantly decreased. Ovarian reserve was not affected from the medication, in addition RA have induced reproductive capacity.

 

 

 

Hinyokika Kiyo. 2012 Jul;58(7):329-33. Review. Japanese.

Mixed type ureteral endometriosis : a case report and a review of the Japanese literature.

Kurobe M1Kojima TUchida MMiyagawa TTsutsumi MSugita S.

 

Abstract

Ureteral endometriosis is a rare but important clinical problem that requires early detection and treatment. The urinary tract is affected in approximately 2% of women with endometriosis. Even though the bladder is the most frequent urinary tract organ affected in these patients,the ureter is also affected in 10-40% of the cases, thus requiring immediate clinical attention. The majority of endometrial lesions is typically located in the lower segment of the ureter and is often difficult to differentiate between endometriosis and malignancy. Ureteral endmetriosis should be considered for women with hydronephrosis. In this report we present one clinical case of mixed-type ureteral endometriosis. A 37-year-old woman was referred to our hospital due to left hydronephrosis. Contrast-enhanced CT scan confirmed left hydronephrosis and also showed a solid mass at the left lower ureter. Retrograde pyelography revealed stenosis of the left lower ureter and Renogram revealed severely impaired renal function. Laparoscopic nephroureterectomy was performed. Pathologically, mixed-type endometriosis of the left ureter was diagnosed.

 

 

 

Int Urogynecol J. 2013 Apr;24(4):565-71. doi: 10.1007/s00192-012-1917-6. Epub 2012 Aug 16.

Association of bladder pain syndrome/interstitial cystitis with urinary calculus: a nationwide population-based study.

Keller J1Chen YKLin HC.

 

Abstract

INTRODUCTION AND HYPOTHESIS:

Although one prior study reported an association between bladder pain syndrome/interstitial cystitis (BPS/IC) and urinary calculi (UC), no population-based study to date has been conducted to explore this relationship. Therefore, using a population-based data set in Taiwan, this study set out to investigate the association between BPS/IC and a prior diagnosis of UC.

METHODS:

This study included 9,269 cases who had received their first-time diagnosis of BPS/IC between 2006 and 2007 and 46,345 randomly selected controls. We used conditional logistic regression analysis to compute the odds ratio (OR) and its corresponding 95 % confidence interval (CI) for having been previously diagnosed with UC between cases and controls.

RESULTS:

There was a significant difference in the prevalence of prior UC between cases and controls (8.1 vs 4.3 %, p < 0.001). Conditional logistic regression analysis revealed that cases were more likely to have been previously diagnosed with UC than controls (OR = 1.70; 95 % CI = 1.56-1.84) after adjusting for chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, and asthma. BPS/IC was found to be significantly associated with prior UC regardless of stone location; the adjusted ORs of kidney calculus, ureter calculus, bladder calculus, and unspecified calculus when compared to controls were 1.58 (95 % CI = 1.38-1.81), 1.73 (95 % CI = 1.45-2.05), 3.80 (95 % CI = 2.18-6.62), and 1.83 (95 % CI = 1.59-2.11), respectively.

CONCLUSIONS:

This work generates the hypothesis that UC may be associated with BPS/IC.

 

 

BJOG. 2012 Nov;119(12):1538-43. doi: 10.1111/j.1471-0528.2012.03466.x. Epub 2012 Aug 20.

Pregnancy outcome in women with peritoneal, ovarian and rectovaginal endometriosis: a retrospective cohort study.

Vercellini P1Parazzini FPietropaolo GCipriani SFrattaruolo MPFedele L.

 

Abstract

We retrospectively assessed pregnancy outcome in 419 women who achieved a first spontaneous singleton pregnancy after surgery for endometriosis. A miscarriage was observed in 87 of 419 women (20.8%) and an ectopic pregnancy in eight (1.9%). Among the remaining 324 women, 14 (4.3%) experienced gestational hypertension/pre-eclampsia, 38 (11.7%) had a preterm delivery, five (1.5%) had placental abruption and 12 (3.7%) had placenta praevia. The incidence of placenta praevia was 7.6% in 150 women with rectovaginal lesions, 2.1% in 69 with ovarian endometriomas plus peritoneal implants, and 2.4% in 100 women with peritoneal implants only, whereas no case was observed in 100 women with ovarian endometriomas only.

 

 

BJOG. 2012 Nov;119(12):1447-54. doi: 10.1111/j.1471-0528.2012.03474.x. Epub 2012 Aug 20.

The risk of vesicovaginal and urethrovaginal fistula after hysterectomy performed in the English National Health Service–a retrospective cohort study examining patterns of care between 2000 and 2008.

Hilton P1Cromwell DA.

 

Abstract

OBJECTIVE:

To estimate rates of vesicovaginal and urethrovaginal fistula among women undergoing hysterectomy by indication and type of procedure, and to assess trends in risk over time.

DESIGN:

Retrospective cohort using data from Hospital Episode Statistics.

SETTING:

English National Health Service (NHS) hospitals.

POPULATION:

Women undergoing hysterectomy for selected common conditions in English NHS hospitals between January 2000 and December 2008.

METHODS:

Unadjusted rates of urogenital fistula were calculated by type of procedure and indication. Logistic regression was used to assess whether the risk of fistula was associated with age, or had changed over time.

MAIN OUTCOME MEASURE:

Rate of urogenital fistula (vesicovaginal and urethrovaginal fistula) within 1 year of hysterectomy.

RESULTS:

Among 343 771 women undergoing hysterectomy, the overall rate of fistula was 1 in 788. The rate varied by indication and procedure, being highest following radical hysterectomy for cervical cancer (1 in 87; 95% CI 61-128) and lowest following vaginal hysterectomy for prolapse (1 in 3861; 95% CI 2550-6161). After total abdominal hysterectomy for endometriosis, menstrual problems or fibroids, the risk of fistula was lower in women aged 50 years or over than in women under 40 years (adjusted odds ratio 0.61; 95% CI 0.38-0.98). The overall rate of fistula increased by 46% during the study period.

CONCLUSIONS:

The risk of urogenital fistula was associated with type of hysterectomy and indication; the risk increased during the study period, and was lower after hysterectomy for benign conditions in women aged 50 years or over.

 

 

 

Gynecol Obstet Fertil. 2012 Sep;40(9):494-6. doi: 10.1016/j.gyobfe.2012.07.009. Epub 2012 Aug 15. Review. French.

Animal models in endometriosis experimental research.

Colette S1Donnez J.

 

Abstract

Sampson’s menstrual reflux theory is commonly used to explain the origin of endometriotic lesions in women. However, their pathogenesis remains largely unknown. Validated research models need to be developed with the aim of studying mechanisms by which endometrial cells from menstrual reflux implant and grow, and investigating if potential new markers or molecules could be envisaged as diagnostic or therapeutic tools. The present review looks at the different existing murine and non-human primate models of endometriosis, and evaluates their principal uses.

 

 

Fertil Steril. 2012 Nov;98(5):1218-24.e1-2. doi: 10.1016/j.fertnstert.2012.07.1117. Epub 2012 Aug 15.

Interleukin-17A is present in neutrophils in endometrioma and stimulates the secretion of growth-regulated oncogene-α (Gro-α) from endometrioma stromal cells.

Takamura M1Osuga YIzumi GYoshino OKoga KSaito AHirata THirota YHarada MHasegawa ATaketani Y.

 

Abstract

OBJECTIVE:

To investigate a new role of interleukin (IL)-17A in endometriosis.

DESIGN:

Laboratory study.

SETTING:

University hospital.

PATIENT(S):

Patients with ovarian endometrioma undergoing laparoscopy or laparotomy.

INTERVENTION(S):

Primary culture of endometrioma stromal cells (EoSCs) was stimulated with IL-17A. Sections of endometrioma tissue were immunostained with antibodies for IL-17A, growth-regulated oncogene-α (Gro-α), and elastase, a marker of neutrophils. They were also examined with immunofluorescent double staining for IL-17A and myeloperoxidase, another marker of neutrophils.

MAIN OUTCOME MEASURE(S):

Concentration of Gro-α was measured using a specific ELISA. Neutrophil chemotaxis was measured with Boyden chamber method. Immunostained sections were examined under microscope.

RESULT(S):

Interleukin-17A increased the secretion of Gro-α from EoSCs dose-dependently. The conditioned medium of EoSCs stimulated with IL-17A attracted more neutrophils than that of EoSCs stimulated with vehicle, and the increase was inhibited by the addition of Gro-α-neutralizing antibody. On immunostaining, IL-17A and Gro-α were detected in similar areas of the stroma beneath the epithelium, where Gro-α was detected in cells with a stromal cell appearance whereas IL-17A was detected in neutrophils as determined by detection of elastase. Fluorescent immunostaining corroborated that myeloperoxidase-positive neutrophils were also positive for IL-17A.

CONCLUSION(S):

It is suggested that IL-17A produced by neutrophils stimulates Gro-α secretion from EoSCs, thereby recruiting more neutrophils and inducing perpetuating inflammation in endometriosis.

 

 

Hum Immunol. 2012 Nov;73(11):1190-3. doi: 10.1016/j.humimm.2012.08.008. Epub 2012 Aug 16.

The nuclear factor-kB functional promoter polymorphism is associated with endometriosis and infertility.

Bianco B1Lerner TGTrevisan CMCavalcanti VChristofolini DMBarbosa CP.

 

Abstract

INTRODUCTION:

An aberrant immunologic mechanism has been suggested to be involved in the pathogenesis of endometriosis. Nuclear factor-kB (NF-kB) plays a key role in the immune and inflammatory response and modulates cell proliferation, apoptosis, adhesion, invasion, and angiogenesis in many cell types involved in the development of endometriosis. We hypothesized a possible relationship between the NFKB1 promoter regulatory polymorphism and endometriosis and/or infertility.

METHODS:

A genetic association study comprising 172 infertile women with endometriosis, 77 women with idiopathic infertility and 189 controls was performed. Detection of the -94 insertion/deletion ATTG (rs28362491) polymorphism in the NFKB1 gene was done using the RFLP-PCR (Restriction Fragment Length Polymorphism-Polymerase Chain Reaction) technique. The results were statistically analyzed, and a p-value <0.05 was considered significant.

RESULTS:

Single-marker analysis revealed a significant association between the -94 insertion/deletion ATTG polymorphism and endometriosis-related infertility (p=0.014, OR=1.47, 95% CI=1.09-1.97), especially in moderate/severe disease cases. Considering the idiopathic infertility group, a significant association was also found (p=<0.001, OR=2.01, 95% CI=1.35-2.98), suggesting that the -94 insertion/deletion ATTG polymorphism is associated with endometriosis and/or infertility.

CONCLUSION:

In the population sample studied, the -94 insertion/deletion ATTG polymorphism in the NFKB1 gene was positively associated both with moderate/severe endometriosis and idiopathic infertility.

 

 

Gynecol Obstet Fertil. 2012 Sep;40(9):497-9. doi: 10.1016/j.gyobfe.2012.07.019. Epub 2012 Aug 17. French.

Who should treat the endometriosic infertile patient? The ART technician, the surgeon, or the psychiatrist?.

Lachowsky M1.

 

Abstract

The answer is simpler than the question ! Endometriosis and infertility, a heavy burden: psychological and physical pains do not simply add but potentialise each other, especially when hard life-events have already darkened the past. All the more difficult for these women who have long felt they were considered as nervous and “hysterical”, and not as “real” patients, despite their effective and now well-known painful symptoms. They will recover their dignity if we, health practitioners, recognize their right and their need to be taken in charge by a multidisciplinary team, in a psychosomatic approach. Every specialist will, each with his own means, work for their health, meaning the present and future well-being of those endometriosic infertile women.

 

 

Clin Exp Obstet Gynecol. 2012;39(2):191-4.

Clinicopathological changes of uterine leiomyomas after GnRH agonist therapy.

Grigoriadis C1Papaconstantinou EMellou AHassiakos DLiapis AKondi-Pafiti A.

 

Abstract

OBJECTIVE:

Gonadotrophin-releasing hormone agonist (GnRHa) has been commonly used for the medical treatment of prostate cancer, precocious puberty, endometriosis, adenomyosis and uterine leiomyomas. GnRHa therapy in cases of symptomatic uterine leiomyomas aims for the reduction of their size and remission of symptoms such as menometrorrhagia, causing a state of hypoestrogenemia. This is considered to be a helpful preoperative strategy in cases of large myomas, or anemia because of abnormal vaginal bleeding. The aim of this retrospective study was to examine the clinicopathological changes in uterine leiomyomas exposed to preoperative GnRHa therapy for two up to six months.

MATERIALS AND METHODS:

The study group consisted of 10 premenopausal patients who were treated with GnRHa prior to surgery.

RESULTS:

In all cases the size of leiomyomas was reduced after GnRHa therapy. A microscopic review of the surgical specimens showed increased cellularity and ischemic type of necrosis.

CONCLUSION:

Morphological changes of uterine leiomyomas are often associated with preoperative GnRH agonist therapy. The differential diagnosis from uterine leiomyosarcomas includes absence of mitotic activity.

 

 

Clin Exp Obstet Gynecol. 2012;39(2):229-33.

Effects of estrogen and progestin on expression of MMP-2 and TIMP-2 in a nude mouse model of endometriosis.

Wang J1Ma X.

 

Abstract

OBJECTIVE:

The study endeavored to observe the effects of estrogen and progestin on expression of matrixmetalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in a nude mouse model of endometriosis (EMT) and to explore the roles of MMP-2/TIMP-2 in the pathogenesis of EMT.

METHODS:

Sixty nude mice were injected in the abdominopelvic cavity with human endometrial tissue and randomly divided into four hormone treatment groups (estrogen, progestin, estrogen+progestin, and saline control; n=15 per group). Implantation rates and gross morphological characteristics were assessed. Further, expression of MMP-2 and TIMP-2 in ectopic endometrial lesions was detected by immunohistochemistry.

RESULTS:

The overall implantation rate of endometrial samples was 87.5% (50/60) in injected nude mice. Although there was no statistically significant difference in implantation rates between groups, the number of lesions in the progestin group was higher than that in other groups, and the size of lesions in the progestin and estrogen+progestin groups was larger than in the estrogen and control groups (p < 0.05). Further, expression levels of MMP-2 in the estrogen and estrogen+progestin groups were higher than in the progestin and control groups (p < 0.05). In contrast, expression levels of TIMP-2 in estrogen, progestin, and estrogen+progestin groups were lower than in the control group; additionally, the expression level of TIMP-2 in the progestin group was lower than in the estrogen group (p < 0.05). Finally, the ratios of MMP-2/TIMP-2 expression in the estrogen, progestin, and estrogen+progestin groups were higher than for the control group; in fact, this ratio was highest in the estrogen+progestin group (p < 0.05).

CONCLUSIONS:

The nude mouse is an appropriate model for early clinical studies of EMT, specifically in the detection of MMP-2 and TIMP-2. These proteins appear important in the pathogenesis of EMT. Specifically, estrogen can raise the expression level of MMP-2 to promote ectopic implantation of endometrial tissue. Meanwhile, progestin can inhibit the expression of TIMP-2 to raise the MMP-2/TIMP-2 ratio, which can enhance invasiveness of ectopic endometrium to promote implantation.

 

 

Clin Exp Obstet Gynecol. 2012;39(2):265-8. Review

A rare case of intrinsic ureteral endometriosis causing hydronephrosis in a 40-year-old woman. A case report and literature review.

Papakonstantinou E1Orfanos FMariolis-Sapsakos TVlahodimitropoulos DKondi-Pafiti A.

 

Abstract

Endometriosis is a multifactorial disease with unclear pathogenesis. Urinary tract endometriosis occurs in about 1% of all endometriotic lesions while isolated ureteral endometriosis is extremely rare. We present a case of intrinsic ureteral endometriosis causing ureteral stenosis in a 40-year’s old woman, in combination with intestinal, extensive peritoneal and ovarian endometriosis. The clinicopathological features and investigation methods used, as well as the treatment approach are discussed. An individual therapy plan depending mainly on the patient’s age, desire for children and the extent of the endometriotic foci should always be attempted. Collaboration between gynecologists and urologists was essential in our cases.

 

 

JSLS. 2012 Jan-Mar;16(1):140-2. doi: 10.4293/108680812X13291597716384.

Bilateral thoracic endometriosis affecting the lung and diaphragm.

Nezhat C1King LPPaka COdegaard JBeygui R.

 

Abstract

INTRODUCTION:

Endometriosis of the lung and the diaphragm is rare. Patients may present with symptoms such as shortness of breath, chest pain, and shoulder pain or they may be asymptomatic. Of note, there have been few reports of bilateral catamenial disease, and no reports, to our knowledge, of bilateral pathology proven pulmonary parenchymal endometriosis.

CASE:

A 43-year-old with stage IV endometriosis and large leiomyoma underwent a laparoscopic hysterectomy and treatment of endometrial lesions in 2005. In March and April of 2011, she presented with bilateral pneumothoraces. She subsequently underwent video-assisted thoracoscopy as well as resection and fulguration of bilateral lung and diaphragmatic endometriosis. Pathology confirmed endometrial implants in the lung parenchyma bilaterally.

CONCLUSION:

Catamenial pneumothorax is the most common presentation of thoracic endometriosis. However, bilateral catamenial pneumothoraces are rare. To the best of our knowledge, this case reflects the first report of pathology proven bilateral lung and diaphragm endometriosis.

 

 

Fertil Steril. 2012 Dec;98(6):1503-11.e1. doi: 10.1016/j.fertnstert.2012.07.1129. Epub 2012 Aug 19.

“I can’t get no satisfaction”: deep dyspareunia and sexual functioning in women with rectovaginal endometriosis.

Vercellini P1Somigliana EBuggio LBarbara GFrattaruolo MPFedele L.

 

Abstract

OBJECTIVE:

To assess the impact of rectovaginal endometriosis on pain at intercourse and sexual functioning.

DESIGN:

Case-control study.

SETTING:

Academic department.

PATIENT(S):

Case subjects were women with rectovaginal endometriosis (n = 100), and control subjects were women with a surgical diagnosis of peritoneal and/or ovarian endometriosis (n = 100) or without endometriosis (n = 100).

INTERVENTION(S):

Questionnaires (visual analogue scale [VAS] and revised Sabbatsberg Sexual Self-Rating Scale [SRS]).

MAIN OUTCOME MEASURE(S):

Frequency and severity of deep dyspareunia and sexual functioning.

RESULT(S):

Deep dyspareunia was reported by 67/100 (67%) women in the rectovaginal endometriosisgroup, 52/99 (53%) in the peritoneal and/or ovarian endometriosis group, and 24/93 (26%) in the nonendometriosis group. Mean ± SD dyspareunia VAS scores were, respectively, 44 ± 34, 30 ± 32, and 13 ± 26. Women in both endometriosis groups performed significantly worse than those in the nonendometriosis group in several SRS subdomains. No significant difference in overall SRS score was detected between women in the two endometriosis groups.

CONCLUSION(S):

Women with endometriosis experienced more frequent and severe deep dyspareunia and worse sexual functioning compared with women without endometriosis, whereas differences between women with diverse endometriosis forms were marginal.

 

 

Gynecol Oncol. 2012 Nov;127(2):398-402. doi: 10.1016/j.ygyno.2012.08.013. Epub 2012 Aug 19

Analysis of common variations in tumor-suppressor genes on chr1p36 among Caucasian women with endometriosis.

Falconer H1Sundqvist JXu HVodolazkaia AFassbender AKyama CBokor AD’Hooghe TM.

 

Abstract

OBJECTIVE:

Epidemiological data indicate that endometriosis increases the risk of epithelial ovarian cancer (EOC), but the mechanism of cancer transition is unknown. Results from genome-wide association studies (GWAS) and transcriptome sequencing have demonstrated that genes located in the 1p36 region are important in both endometriosis and endometriosis-associated cancer development. Therefore, we tested the hypothesis that SNPs in two tumor-suppressor genes (CHD5 and ARID1A) in the 1p36 region are associated with endometriosis.

METHODS:

Allele frequencies of SNPs were investigated in 1685 Caucasian women consisting of 947 women with endometriosis and 738 controls. Peripheral blood samples were retrieved, DNA extracted and allelic frequencies of SNPs in two tumor-suppressor genes (CHD5 and ARID1A) were analyzed using TaqMan Open Array technique.

RESULTS:

Associations were observed for 3 SNPs in the CHD5 gene: rs1883603 (OR 1.31, 95% CI 1.00-1.71), rs9434741 (OR 1.41, 95% CI 1.16-1.71) and rs17436816 (OR 1.24, 95% CI 1.02-1.50). After correction for multiple comparisons, rs9434741 (CHD5) remained significantly associated with endometriosis (p<0.01). No associations were detected for ARID1A.

CONCLUSIONS:

In this Caucasian population, endometriosis seems to be associated with the tumor-suppressor gene CHD5. Our findings support recent data, suggesting that the 1p36 region plays an important role in endometrios. To validate these data, replication in an independent population is warranted.

 

 

PLoS One. 2012;7(7):e41080. doi: 10.1371/journal.pone.0041080. Epub 2012 Jul 20.

miRNA signature and Dicer requirement during human endometrial stromal decidualization in vitro.

Estella C1Herrer IMoreno-Moya JMQuiñonero AMartínez SPellicer ASimón C.

 

Abstract

Decidualization is a morphological and biochemical transformation of endometrial stromal fibroblast into differentiated decidual cells, which is critical for embryo implantation and pregnancy establishment. The complex regulatory networks have been elucidated at both the transcriptome and the proteome levels, however very little is known about the post-transcriptional regulation of this process. miRNAs regulate multiple physiological pathways and their de-regulation is associated with human disorders including gynaecological conditions such as endometriosis and preeclampsia. In this study we profile the miRNAs expression throughout human endometrial stromal (hESCs) decidualization and analyze the requirement of the miRNA biogenesis enzyme Dicer during this process. A total of 26 miRNAs were upregulated and 17 miRNAs downregulated in decidualized hESCs compared to non-decidualized hESCs. Three miRNAs families, miR-181, miR-183 and miR-200, are down-regulated during the decidualization process. Using miRNAs target prediction algorithms we have identified the potential targets and pathways regulated by these miRNAs. The knockdown of Dicer has a minor effect on hESCs during in vitro decidualization. We have analyzed a battery of decidualization markers such as cell morphology, Prolactin, IGFBP-1, MPIF-1 and TIMP-3 secretion as well as HOXA10, COX2, SP1, C/EBPß and FOXO1 expression in decidualized hESCs with decreased Dicer function. We found decreased levels of HOXA10 and altered intracellular organization of actin filaments in Dicer knockdown decidualized hESCs compared to control. Our results provide the miRNA signature of hESC during the decidualization process in vitro. We also provide the first functional characterization of Dicer during human endometrial decidualization although surprisingly we found that Dicer plays a minor role regulating this process suggesting that alternative biogenesis miRNAs pathways must be involved in human endometrial decidualization.

Obstet Gynecol. 2012 Jul;120(1):104-12.

Interrater and intrarater reliability in the diagnosis and staging of endometriosis.

Schliep KC1Stanford JBChen ZZhang BDorais JKBoiman Johnstone EHammoud AOVarner MWLouis GMPeterson CM.

 

Abstract

OBJECTIVE:

To estimate the interrater and intrarater reliability of endometriosis diagnosis and severity of disease among gynecologic surgeons viewing operative digital images.

METHODS:

The study population comprised a random sample (n=148 [36%]) of women who participated in the Endometriosis: Natural History, Diagnosis and Outcomes study. Four academic expert and four local, specialized expert surgeons reviewed the images, diagnosed the presence or absence of endometriosis for each woman, and rated severity using the revised American Society for Reproductive Medicine (ASRM) criteria. Interrater-level and intrarater-level agreement were calculated for both endometriosis diagnosis and staging.

RESULTS:

The interrater reliability for endometriosis diagnosis among the eight surgeons was substantial: Fleiss κ=0.69 (95% confidence interval [CI] 0.64-0.74). Surgeons agreed on revised ASRM endometriosisstaging criteria after experienced assessment in a majority of cases (mean 61%, range 52-75%) with moderate interrater reliability: Fleiss κ=0.44 (95% CI 0.41-0.47). The intrarater reliability for experienced assessment compared with computer-assisted revised ASRM staging was almost perfect (mean weighted κ=0.95, range 0.89-0.99).

CONCLUSION:

Substantial reliability was found for revised ASRM endometriosis diagnosis, whereas moderate reliability was observed for staging. Almost perfect reliability was observed for surgeons’ rating of disease severity compared with computerized-assisted, checklist-based staging. Findings suggest that reliability in endometriosis diagnosis is not greatly altered by location or composition of surgeons, supporting the conduct of multisite studies or compilation of endometriosis data across clinical centers. Although surgeons appear to be skilled at assessing endometriosis stage intuitively, how staging of disease burden correlates with clinical outcomes remains to be developed.

 

Obstet Gynecol. 2012 Sep;120(3):581-6. doi: 10.1097/AOG.0b013e3182638c3a.

Risk factors for postoperative urinary retention after laparoscopic and robotic hysterectomy for benign indications.

Smorgick N1DeLancey JPatzkowsky KAdvincula ASong AAs-Sanie S.

 

Abstract

OBJECTIVE:

To estimate the occurrence of postoperative urinary retention after traditional laparoscopic and robotic hysterectomy.

METHODS:

We performed a chart review of all patients who underwent total or supracervical hysterectomy using a laparoscopic (n=253) or robotic approach (n=281) from March 2001 until June 2010 for benign indications at the division for minimally invasive surgery. Urinary retention was defined as the inability to spontaneously void or as incomplete voiding requiring either self-catheterization or Foley catheter replacement in the first postoperative week.

RESULTS:

Urinary retention occurred in 7.3% (95% confidence interval [CI] 5.2-9.8%) of women and was more than twice as common among women who underwent robotic hysterectomy compared with laparoscopic hysterectomy (10.3%, 95% CI 7.0-14.5% compared with 4.0%, 95% CI 1.9-7.1%, P=.005). No statistically significant differences in those with and without urinary retention were seen in age, body mass index, smoking status, number of prior cesarean deliveries, operative time, presence of severe adhesions, or findings of endometriosis. In a multivariable logistic regression analysis, only the robotic approach relative to traditional laparoscopic approach was found to be significantly associated with urinary retention (odds ratio 2.6, 95% CI 1.2-5.6). Postoperative urinary retention was associated with a higher incidence of lower urinary tract infection, occurring in 15.4% (95% CI 5.9-30.5%) of cases compared with 4.0% (95% CI 2.5-6.2%) of those without urinary retention (P=.008).

CONCLUSION:

Transient urinary retention is relatively more common after robotic hysterectomy when compared with laparoscopic hysterectomy. We postulate that more aggressive bladder dissection performed with robot assistance may be associated with an increased risk of urinary retention.

 

 

Reprod Sci. 2013 Jan;20(1):78-84. doi: 10.1177/1933719112451146. Epub 2012 Aug 20.

Epigenetic disorder may cause downregulation of HOXA10 in the eutopic endometrium of fertile women with endometriosis.

Lu H1Yang XZhang YLu RWang X.

 

Abstract

HOXA10 is an important gene for endometrial receptivity and plays a regulatory role in the adult female reproductive tract. It is regulated by epigenetic modulation in the CpG clusters of promoter in some cases. The aim of this study was to investigate HOXA10 expression and the epigenetic regulation in the eutopic endometrium of fertile women with endometriosis by quantitative real-time polymerase chain reaction (RT-PCR) and Western blot. The effect of 5-azacytidine (5-ac), a demethylation agent on HOXA10 expression was determined on endometrium stromal cells (ESCs) from these women with endometriosis. Results revealed that in normal endometrium (NE), HOXA10 messenger RNA (mRNA) and protein expression at the secretory phase were significantly higher than that at the proliferative phase. The HOXA10 mRNA and protein expression in the eutopic endometrium of endometriosis were significantly lower than in NE. The HOXA10 mRNA and protein levels in cultured stromal cells from endometriosis in vitro were significantly increased in a 5-ac treatment group compared with a nontreatment group. Our results indicated that the level of HOXA10 decrease in the eutopic endometrium of patients with endometriosis. Upregulation of HOXA10 in ESCs after treatment with 5-ac suggests that HOXA10 expression is controlled by methylation of the promoter. An epigenetic aberration is likely the main cause of endometriosis.

 

 

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