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Clin Exp Obstet Gynecol. 2012;39(4):526-8.
Evaluation of utero-ovarian hemodynamics in relation to fertility and stage of 
endometriosis.

Anicic R1Djukic MRakic SVasiljevic MDimitrijevic DMilicevic S.

 

Abstract

OBJECTIVE:

The aim of this study was to compare hemodynamic changes in the uterine and ovarian arteries between infertile women with moderate and/or severe endometriosis and healthy women. In this prospective study, 99 women in their generative age were subjected to color Doppler ultrasonography to measure hemodynamic parameters from July 2010 to January 2011. The examination was performed during the proliferative or ovulatory phase of the natural menstrual cycle in a random sample of 54 women treated for endometriosis-induced infertility and 45 healthy women were included in control examination procedure. Irrespective of considered stage, endometriosis was most often found in the ovaries, in the sacro-uterine ligaments, peritoneum, and rectovaginally. Resistance to blood flow expressed as the resistance index (RI) in the measured arteries, was significantly higher in severe endometriosis compared to moderate form. Average values of pulsation index (PI) and RI are significantly higher, in both endometriosis stages, compared to measured values in healthy women.

 

 

Clin Exp Obstet Gynecol. 2012;39(4):562-4.

Primary umbilical endometriosis: case report and literature review.

Minaidou E1Polymeris AVassiliou JKondi-Paphiti AKaroutsou EKatafygiotis PPapaspyrou E.

 

Abstract

We present a case of primary endometriosis of the umbilicus in a young nulliparous patient without any previous history of abdominal or pelvic surgery. Primary endometriosis of extra pelvic sites is unusual while umbilical endometriosis is quite rare. Diagnosis of endometriosis is difficult to obtain and sometimes diagnoses can be false-positive or false-negative. Some imaging procedures can be done to rule out other disorders but it is difficult to differentiate them from endometriosis. A definite diagnosis can only be established by histopathological examination. Hematoxylin and eosin (H&E) is the staining of choice. Conservative surgical excision of the lesion and drugs such as oral contraceptives and gonadotropin releasing analogues are the first-line treatment.

 

 

 

Gen Thorac Cardiovasc Surg. 2014 Mar;62(3):198-201. doi: 10.1007/s11748-013-0227-3. Epub 2013 Feb 28.

Intrathoracic papillary thyroid carcinoma from occult primary disease.

Oikonomou A1Astrinakis EGiatromanolaki AKarros PMargaritis DPrassopoulos P.

 

Abstract

A 42-year-old woman undertook a chest radiograph for a routine evaluation prior to surgery for pelvic endometrioma, which revealed a right paratracheal mass slightly displacing the trachea to the left. CT of the thorax disclosed a well demarcated, heterogeneous, lobular, right paratracheal mass, bearing punctate, coarse, and curvilinear calcifications. MRI further revealed two components within the lesion: a larger, cystic, exhibiting thin septations, and a solid component at the lower part exhibiting strong enhancement. No continuity of the mass with the thyroid gland was demonstrated, which had normal size and no focal lesion. Histological examination of the resected mass disclosed lymph node tissue infiltrated by papillary thyroid carcinoma; subsequent total thyroidectomy revealed small foci of papillary carcinoma within both lobes of the thyroid gland. Ablative dose I-131 was administered and the patient was put on daily thyroid supplements.

 

 

Semin Reprod Med. 2013 Mar;31(2):101-8. doi: 10.1055/s-0032-1333475. Epub 2013 Feb 27.

Adenomyosis and subfertility: evidence of association and causation.

Tomassetti C1Meuleman CTimmerman DD’Hooghe T.

 

Abstract

Due to the confounding or unknown presence of endometriosis in both cases and controls, it is difficult to test the hypothesis that adenomyosis causes infertility. Based on the limited available evidence, there is evidence to support a causal association between adenomyosis and subfertility: Adenomyosis is associated with lifelong infertility in baboons, is associated with impaired reproductive outcome after assistive reproductive technique, and a dose-effect relationship between the degree of adenomyosis and the degree of abnormal uterotubal contractility has been demonstrated. More and better designed studies are needed to assess the impact of adenomyosis on infertility in women with the laparoscopic-proven presence or absence of endometriosis.

 

 

 

 

Semin Reprod Med. 2013 Mar;31(2):109-24. doi: 10.1055/s-0032-1333476. Epub 2013 Feb 27.

Eutopic endometrium in women with endometriosis: ground zero for the study of implantation defects.

Lessey BA1Lebovic DITaylor RN.

 

Abstract

The endometrium is ground zero when it comes to understanding how implantation occurs and how it might also fail, resulting in infertility or pregnancy loss. Many of the causes of diminished uterine receptivity are acquired during a woman’s lifetime. Endometriosis, a major inflammatory disease affecting women, is also a leading cause of infertility and miscarriage. Once established, the inflammatory changes can, in some women, lead to progesterone resistance and downstream changes in endometrial gene expression. Much is now known about how inflammation translates to progesterone resistance and infertility, but much remains to be learned. In this review we provide an overview for understanding how the endometrium becomes dysfunctional, what biomarkers may hold promise for the diagnosis of endometriosis, and how progesterone resistance leads to infertility. Understanding the pathophysiology of this disease will likely lead to better treatment options.

 

 

Semin Reprod Med. 2013 Mar;31(2):125-32. doi: 10.1055/s-0032-1333477. Epub 2013 Feb 27.

Translational animal models to study endometriosis-associated infertility.

Grümmer R1.

 

Abstract

Although there is an apparent association between endometriosis and impaired fertility, the pathophysiology of the reduced fecundity in women with endometriosis still remains unclear. Reproduction is a complex and multifactorial process, and possible factors contributing to the reduced fertility of endometriosis patients include defective function of the ovary, gametes, and endometrium as well as developmental disorders of the embryo. Because controlled experiments in humans are limited due to ethical reasons, experimental animal models have been developed mainly in nonhuman primates and laboratory rodents by induction of endometriosis via autologous transplantation of endometrial tissue. Animals with induced endometriosis reveal an impairment of fecundity similar to the situation described for humans and have been used to identify effects of ectopic endometrial tissue on adhesion formation, peritoneal fluid composition, ovarian function, endometrial gene expression, and embryo implantation. These animal models of endometriosis yield a valuable tool to study the mechanisms of endometriosis-associated infertility especially during the onset of the disease that cannot be investigated in women.

 

 

Semin Reprod Med. 2013 Mar;31(2):133-43. doi: 10.1055/s-0032-1333478. Epub 2013 Feb 27.

Role of surgery in endometriosis-associated subfertility.

Berlanda N1Vercellini PSomigliana EFrattaruolo MPBuggio LGattei U.

 

Abstract

Analysis of published series reveals that no more than a fourth of subfertile patients undergoing surgery for peritoneal endometriotic implants, rectovaginal endometriotic lesions, or recurrent endometriomas achieved conception spontaneously. First-line surgery for ovarian endometriotic cysts appears associated with a better reproductive performance, that is, a mean postoperative pregnancy rate of ∼50%. At the same time, excision of endometriomas paradoxically seems to induce gonadal damage. With the exception of peritoneal disease, no randomized trials are available to assess the effect of surgery in subfertile women with endometriosis. Therefore, it is not possible to define the absolute benefit increase of the treatment of ovarian and rectovaginal lesions. The decision to undergo surgery for endometriosis-associated subfertility must be shared with the woman after detailed information and taking into account several additional conditions, such as presence of pain, large or complex adnexal masses, bowel or ureteral stenosis, and coexisting infertility factors. When considering surgery, a therapeutic equipoise should be reached that includes demonstrated benefits, potential morbidity, and costs of treatment alternatives. Particularly in case of recurrent endometriosis, in vitro fertilization should generally be preferred to surgery. The role of surgery in endometriosis-associated subfertility includes temporary pain relief in symptomatic women desiring a spontaneous conception.

 

 

Semin Reprod Med. 2013 Mar;31(2):144-9. doi: 10.1055/s-0032-1333479. Epub 2013 Feb 27.

Diminished ovarian reserve and endometriosis: insult upon injury.

Shah DK1.

 

Abstract

Endometriosis is a disease that affects a significant proportion of reproductive-age women. The impact of the disease on ovarian reserve is an important consideration when planning treatment in women who want to maintain their potential for future childbearing. The existing literature supports an adverse effect of both superficial endometriosis and ovarian endometriomas on ovulation rates, markers of ovarian reserve, and response to ovarian stimulation, although data on clinical pregnancy and live-birth rates remain inconsistent. Surgical treatment of endometriomas may further worsen ovarian responsiveness by inadvertently removing healthy ovarian tissue or compromising vascular supply to the ovary. Although the evidence overall supports a role for surgery in improving spontaneous pregnancy rates, the question of whether identification of an endometrioma warrants its excision in the subgroup of women undergoing infertility treatment remains a subject of ongoing debate. Many practitioners recommend proceeding directly to in vitro fertilization to reduce time to pregnancy, reserving surgery for women who present with large endometriomas and concomitant symptoms of pain. Further study is required as to the mechanisms by which endometriosis damages ovarian damage as well as the most appropriate treatment in various subpopulations of women with the disease.

 

 

 

Semin Reprod Med. 2013 Mar;31(2):150-3. doi: 10.1055/s-0032-1333480. Epub 2013 Feb 27.

Impact of superovulation for women with endometriosis.

Kavoussi SK1.

 

Abstract

Superovulation (SO)/Intrauterine insemination (IUI) has been used as a treatment approach for endometriosis-associated infertility. The existing medical literature regarding SO in endometriosis patients is composed of heterogeneous studies that differ in terms of study design, SO protocols, the addition of IUI, and comparison groups. There is a need for more well-designed studies to further investigate the efficacy of SO in women with endometriosis-associated infertility. Although in vitro fertilization (IVF) is most effective and is significantly superior to other treatments in endometriosis patients, most of the existing studies suggest some benefit of SO/IUI in infertility patients with early-stage disease. Therefore, SO/IUI is a reasonable early fertility treatment option for women with endometriosis who desire a short trial of potentially more cost-effective treatment options prior to pursuing an IVF cycle and those for whom IVF is not a feasible or desirable option. It appears that gonadotropins are most effective for SO in this patient population even though more head-to-head comparisons are needed.

 

 

 

Semin Reprod Med. 2013 Mar;31(2):154-63. doi: 10.1055/s-0032-1333481. Epub 2013 Feb 27.

Endometriosis and assisted reproductive technologies: maximizing outcomes.

Surrey ES1.

 

Abstract

In vitro fertilization (IVF) represents the most efficient means of overcoming endometriosis-related infertility. Compromised pelvic anatomy and a hostile peritoneal environment are bypassed. Despite the results of early trials, more contemporary outcomes data would suggest that when controlled for age, IVF cycle outcome is not compromised by the presence of endometriosis. One exception to this concept is the finding that patients with ovarian endometriomas demonstrate poorer response to gonadotropin therapy, although it is not clear that this affects the likelihood of implantation. Surgical ablation of superficial endometriosis has no clear impact on IVF pregnancy rates, although a small number of recent trials suggest that pre-cycle resection of deeply infiltrative disease may be beneficial. With the exception of traditional gynecologic indications, there is no evidence to suggest that resection of ovarian endometriomas has any positive impact on cycle outcome. There are, in fact, data demonstrating that resection may exert a deleterious effect on ovarian reserve. A subset of patients will benefit from administration of a prolonged course of a gonadotropin-releasing hormone agonist prior to an IVF cycle. However, the characteristics of that subset have not been identified. It would be logical to consider this approach in women with more advanced disease, severe symptoms, and a history of implantation failure. Data on the impact of other pre-cycle medical interventions such as aromatase inhibitors, danazol, or oral contraceptives are more limited. There is also no evidence to suggest that the ovarian stimulation associated with IVF induces progression of endometriosis.

 

 

 

Semin Reprod Med. 2013 Mar;31(2):164-72. doi: 10.1055/s-0032-1333482. Epub 2013 Feb 27.

Endometriomas and assisted reproductive technology.

Flyckt R1Soto EFalcone T.

 

Abstract

Endometriomas in the assisted reproductive technology patient present a challenging clinical scenario for the infertility specialist. Although surgical management is often pursued in cases of pain or large cyst diameter, patients without such factors must be counseled regarding surgical versus expectant management. Decisions to pursue surgery must be viewed in the context of potentially decreased ovarian reserve and more difficult stimulation for in vitro fertilization. In this article, three distinct cases are presented along with a summary of the most current literature available to guide clinicians in the optimal management of in vitro fertilization patients with endometriomas.

 

 

Semin Reprod Med. 2013 Mar;31(2):173-7. doi: 10.1055/s-0032-1333483. Epub 2013 Feb 27.

Oocyte donation and endometriosis: What are the lessons?

Hauzman EE1Garcia-Velasco JAPellicer A.

 

Abstract

Outcomes of in vitro fertilization cycles in women with endometriosis are significantly worse than in patients without this condition. The impact of endometriosis on ovarian reserve and the quality of retrieved oocytes seems evident. Lower implantation rates, however, raise the question whether this finding is purely the consequence of lower number and poorer quality of embryos, or whether it also reflects compromised endometrial receptivity. Oocyte donation provides an interesting model to investigate reproductive outcome because factors affecting the oocytes are excluded, especially if cycles using oocytes derived from the same donor are analyzed. These studies have shown lower implantation rates in nonendometriotic patients who received oocytes from women with endometriosis, whereas healthy donated oocytes have proven to contribute to a pregnancy with similar chances in women without the disease. The question still to be answered is whether this situation applies for natural cycles or whether it is the use of gonadotropin-releasing hormone analogs and hormonal replacement therapy used for endometrial priming in oocyte recipients that reestablishes an adequate uterine environment. Using a genomic tool based on microarray technology (endometrial receptivity array), the study of differential gene expression in the eutopic endometrium of endometriosis patients undergoing oocyte donation treatment is still underway.

 

 

 

Semin Reprod Med. 2013 Mar;31(2):178-82. doi: 10.1055/s-0032-1333484. Epub 2013 Feb 27

Pregnancy outcomes in women with endometriosis.

Falconer H1.

 

Abstract

The association between endometriosis and subfertility is well known and has been the object of intense research in the last decades. However, the potential association between endometriosis and adverse pregnancy outcome has not been studied until recently. The results from epidemiological studies suggest that endometriosis is associated with preterm birth, preeclampsia, antepartal hemorrhage, and an increase in cesarean delivery. These findings suggest that women with endometriosis may need special care during pregnancy. The underlying mechanisms for the observed associations are unknown, and further studies, both experimental and epidemiological, are necessary.

 

 

Cas Lek Cesk. 2013;152(1):4-14. Review. Czech.

Differential diagnosis of the ileum diseases.

Lukáš K1Dvořák KNovotný AHejdová HMišutková J.

 

Abstract

Inflammation of the ileum – ileitis – is classically connected with Crohn’s disease. But a wide variety of diseases is associated with inflammation of the ileum. These include inflammatory bowel disease, infections, spondyloarthropathies, vascular diseases, drug-related enteritis, infiltration (e.g. sarcoidosis, amyloidosis), postirradiation enteritis, tumors, endometriosis, celiac disease and collagenosis.

 

 

J Clin Endocrinol Metab. 2013 Apr;98(4):1575-82. doi: 10.1210/jc.2012-3010. Epub 2013 Feb 28.

MicroRNA23a and microRNA23b deregulation derepresses SF-1 and upregulates estrogen signaling in ovarian endometriosis.

Shen L1Yang SHuang WXu WWang QSong YLiu Y.

 

Abstract

CONTEXT:

Steroidogenic factor (SF)-1 and its downstream target genes involved in estrogen signaling are aberrantly expressed in ovarian endometriosis.

OBJECTIVE:

Our objective was to explore the microRNA-mediated mechanism controlling aberrant SF-1 expression in ovarian endometriosis.

DESIGN:

Bioinformatics analysis predicted that microRNA23a and microRNA23b (miR23a/b) target the NR5A1 3′-untranslated region. We investigated the relative expression and spatial distribution of miR23a/b and analyzed the relationship between miR23a/b and SF-1 expression in endometriotic tissues.

SETTING:

The study was conducted at the Department of Gynecology and Obstetrics, West China Second University Hospital of Sichuan University.

PATIENTS OR OTHER PARTICIPANTS:

We enrolled 23 women with American Fertility Society stage III-IV ovarian endometriosis and 15 disease-free control subjects.

INTERVENTIONS:

Quantitative real-time RT-PCR, in situ hybridization, cell culture, transfections, and luciferase reporter assays were used in this study.

MAIN OUTCOME MEASURES:

The expression of miR23a/b and SF-1, CYP19A1, and StAR mRNAs; the relationships between miRNAs and SF-1 mRNA levels; and the effect of miR23a/b on SF-1 expression were measured in normal and eutopic endometrial stromal cells (ESCs) and 293T cells.

RESULTS:

Both miR23a and miR23b were downregulated in ectopic and eutopic endometrium, compared with normal endometrium, and their expression was inversely correlated with NR5A1 mRNA levels. SF-1 expression was inhibited by miR23a/b overexpression in eutopic ESCs and upregulated by miR23a/b inhibition in normal ESCs.

CONCLUSIONS:

MiR23a and miR23b are potential biomarkers of ovarian endometriosis. This study provides a novel approach for targeting the mechanisms controlling aberrant local estrogen biosynthesis in endometriosis.

 

 

J Clin Endocrinol Metab. 2013 Apr;98(4):1583-90. doi: 10.1210/jc.2012-3475. Epub 2013 Feb 28.

Interleukin-4 and prostaglandin E2 synergistically up-regulate 3β-hydroxysteroid dehydrogenase type 2 in endometrioma stromal cells.

Urata Y1Osuga YAkiyama INagai MIzumi GTakamura MHasegawa AHarada MHirata THirota YYoshino OKoga KKozuma S.

 

Abstract

CONTEXT:

Endometriosis is a chronic inflammatory disease in which immune response and production of estrogen in endometriotic tissues are involved in the development of the disease. Prostaglandin E2 (PGE2) stimulates aromatase (P450arom) expression in endometrioma stromal cells (ESCs) and increases the production of estrogens. On the other hand, an accumulating amount of evidence suggests that IL-4, a typical Th2 cytokine, plays important roles in the disease.

OBJECTIVE:

The objective of the investigation was to study the effect of IL-4 on the expression of 3β-hydroxysteroid dehydrogenase (HSD3B2), a pivotal enzyme for estrogen production, in ESCs.

DESIGN, PATIENTS, AND MAIN OUTCOME MEASURES:

ESCs were isolated from ovarian endometrioma tissues and cultured with IL-4 and PGE2. CP-690550, a Janus protein tyrosine kinase 3 inhibitor, and HSD3B2 small interfering RNA were added to the culture. Gene expression of HSD3B2 and P450arom was examined by quantitative RT-PCR. Dehydroepiandrosterone (DHEA) was added to the culture, and then the combined enzyme activity of HSD3B2, which converts DHEA to androstenedione, and P450arom, which converts androstenedione to estrone, was examined by measuring estrone concentration in the supernatants with a specific enzyme immunoassay.

RESULTS:

IL-4 increased the expression of HSD3B2 mRNA in a dose-dependent manner. CP-650550 inhibited the IL-4-induced increase in HSD3B2 mRNA expression. PGE2 also increased the expression of HSD3B2 mRNA, and the combination of IL-4 and PGE2 synergistically increased the expression of HSD3B2 mRNA. IL-4 had no effect on the expression of P450arom mRNA, whereas PGE2 increased the expression of P450arom mRNA. Although PGE2 alone increased the production of estrone from DHEA, the combination of IL-4 and PGE2 significantly augmented the production of estrone from DHEA. The enhanced production of estrone by the combination of IL-4 and PGE2 was inhibited by CP-690550 and HSD3B2 small interfering RNA.

CONCLUSIONS:

IL-4 in combination with PGE2 may enhance estrogen production in endometriotic tissues, implying an elaborate mechanism that Th2 immune response augments inflammation-dependent progression of the disease.

 

 

Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2013 Feb;30(1):106-10. doi: 10.3760/cma.j.issn.1003-9406.2013.01.026.

Association of FOXP3 gene polymorphism in Chinese women with endometriosis.

Wu ZY1Wang WWWang TYang RFLi YLi TWang SX.

 

Abstract

OBJECTIVE:

To assess the association between single nucleotide polymorphisms (SNPs) of forkhead box P3 gene (FOXP3) and endometriosis in Chinese Han women from central China.

METHODS:

MassARRAY IPLEX and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) technique was used to determine the genotypes of FOXP3 gene in 314 patients with endometriosis and 358 healthy controls.

RESULTS:

Genotypes of C/T polymorphism for the rs2280883 locus, A/C for the rs3761548 locus, and C/T for the rs3761549 locus were determined. No significant difference was detected in distribution of genotypes CC, CT and TT (P=0.770, OR=0.960; P=0.923, OR=1.013) and frequencies of C and T alleles (P=0.772, OR=0.960; P=0.925, OR=1.013) for rs2280883 and rs3761549 between the two groups. And no significant difference was detected in distribution of genotypes AA, AC and CC (P=0.762, OR=0.958) and frequencies of A and C alleles (P=0.715, OR=0.950) for rs3761548 was detected between the two groups. Based on r-AFS classification, the patients were divided into two groups (respectively with I-II stage and III-IV stage endometriosis). Again, no significant difference was detected in distribution of genotypes CC, CT and TT (P=0.454, OR=1.198, P=0.526, OR=0.909; P=0.220, OR=0.750, P=0.548, OR=1.094) and frequencies of C and T alleles (P=0.473, OR=1.215, P=0.532, OR=0.912; P=0.204, OR=0.737, P=0.558, OR=1.089) for rs22080883 and rs3761549 loci between the two patient groups. No association was found between distribution of genotypes AA, AC and CC (P=0.431, OR=1.211; P=0.508, OR=0.905) and frequencies of A and C alleles (P=0.417, OR=1.226; P=0.516, OR=0.908) for rs3761548 locus between the two patient groups.

CONCLUSION:

Our study has failed to found any association between FOXP3 gene polymorphisms rs2280883, rs3761548 and rs3761549 with endometriosis in Chinese Han patients.

 

 

Arch Pathol Lab Med. 2013 Mar;137(3):371-81. doi: 10.5858/arpa.2012-0076-RA.

Primary adenocarcinoma of the urinary bladder: differential diagnosis and clinical relevance.

Zhong M1Gersbach ERohan SMYang XJ.

 

Abstract

CONTEXT:

Glandular lesions of the urinary bladder include a broad spectrum of entities ranging from completely benign glandular lesions to primary and secondary malignancies. Common benign bladder lesions that exhibit glandular differentiation include cystitis cystica, cystitis glandularis, von Brunn nests, nephrogenic adenoma, intestinal metaplasia, urachal remnant, endometriosis, and prostatic-type polyp. The World Health Organization defines primary adenocarcinoma of the bladder as an epithelial malignancy with pure glandular differentiation without evidence of typical urothelial carcinoma. Malignant lesions that should be included in the differential diagnosis of a primary adenocarcinoma of the bladder include noninvasive and invasive urothelial carcinoma with glandular differentiation and secondary malignancies involving the bladder by direct extension or metastasis. The recognition and distinction of these different entities may be a challenge for pathologists, but they are of great clinical importance.

OBJECTIVE:

To review features of primary bladder adenocarcinoma as well as those entities that need to be differentiated from primary bladder adenocarcinoma, with emphasis on clinical findings, pathologic characteristics, and immunoprofiles.

DATA SOURCES:

Selected original articles published in the PubMed service of the US National Library of Medicine.

CONCLUSIONS:

The accurate diagnosis of adenocarcinoma of the urinary bladder is important and challenging. It has to prompt an extensive clinical workup to rule out other glandular lesions in the urinary bladder, especially the possibility of secondary involvement of the bladder by an adenocarcinoma from a different site.

 

 

Acta Obstet Gynecol Scand. 2013 May;92(5):562-6. doi: 10.1111/aogs.12118. Epub 2013 Mar 19.

Enzian classification: does it correlate with clinical symptoms and the rASRM score?

Haas D1Oppelt PShebl OShamiyeh ASchimetta WMayer R.

 

Abstract

OBJECTIVE:

To assess the extent to which the Enzian classification correlates with the revised American Society for Reproductive Medicine (rASRM) score and clinical symptoms in women with deeply infiltrating endometriosis.

DESIGN:

Retrospective cohort study (Canadian Task Force classification II-2).

SETTING:

Endometriosis competence center specializing in minimally invasive surgery.

PATIENTS:

Between 1 January 2009 and 31 December 2011, a total of 194 women underwent surgery due to deeply infiltrating endometriosis. After histological confirmation, they were classified using the rASRM and Enzian systems. Clinical symptoms were recorded preoperatively.

INTERVENTIONS:

Operative laparoscopy to treat endometriosis.

MAIN OUTCOME MEASURES AND RESULTS:

A clear correlation was seen between grades of severity in the rASRM score and the Enzian classification (p < 0.001). In addition, the rASRM severity grade and clinical symptoms correlated with the locations in the Enzian classification in relation to deeply infiltrating endometriosis. Pain and dysmenorrhea correlated strongly (p = 0.002, p < 0.001) with the severity grade in the Enzian classification.

CONCLUSIONS:

Deeply infiltrating endometriosis is well characterized using the Enzian classification as a supplement to the rASRM score. There is also a clear correlation between the rASRM and Enzian classifications, because of the way in which the disease crosses morphological boundaries. The locations in the Enzian classification correlate partially with clinical symptoms, and the classification’s severity grades correlate substantially with pain and dysmenorrhea. In view of these clinical results, use of the Enzian classification can be recommended as a supplement to the rASRM score for detailed description of endometriosis.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(1):60-3. doi:

The association of PTPN22 polymorphism with endometriosis: effect of genetic and clinical factors.

Gloria-Bottini F1Ammendola MSaccucci PPietropolli AMagrini ABottini E.

 

Abstract

OBJECTIVE:

To investigate the possible effect of clinical and genetic variables on the association between PTPN22 and endometriosis.

METHODS:

PTPN22, ACP₁ and p53 codon 72 genetic polymorphisms and duration of previous pharmacological treatment were studied. The study sample consisted of 132 women hospitalized for endometriosis diagnosed by laparoscopic intervention and histologically confirmed: 359 healthy blood donors were studied as controls. PTPN22, ACP1 and p53 codon 72 genotypes were determined by DNA analysis. Discriminant statistical analysis, logistic regression analysis, chi square of independence, power test and linear correlation were performed using SPSS programs.

RESULTS:

A significant increase of PTPN22 *T allele in endometriosis is observed in women carrying ACP1*C allele, in women carrying p53 codon 72 *Pro allele and in women with prolonged pharmacological treatment.

CONCLUSIONS:

PTPN22 may not be a primary factor in the etiology of endometriosis but may cooperate with clinical and genetic factors influencing susceptibility and clinical course of disease. These new observations point to a multifactorial origin of endometriosis and help to explain the reported differences between human populations concerning the association between PTPN22 and endometriosis.

 

 

 

Am J Obstet Gynecol. 2013 Jun;208(6):451.e1-11. doi: 10.1016/j.ajog.2013.02.040. Epub 2013 Feb 27.

Risk factors associated with endometriosis: importance of study population for characterizing disease in the ENDO Study.

Peterson CM1Johnstone EBHammoud AOStanford JBVarner MWKennedy AChen ZSun LFujimoto VYHediger MLBuck Louis GMENDO Study Working Group.

Collaborators (10)

 

Abstract

OBJECTIVE:

We sought to identify risk factors for endometriosis and their consistency across study populations in the Endometriosis: Natural History, Diagnosis, and Outcomes (ENDO) Study.

STUDY DESIGN:

In this prospective matched, exposure cohort design, 495 women aged 18-44 years undergoing pelvic surgery (exposed to surgery, operative cohort) were compared to an age- and residence-matched population cohort of 131 women (unexposed to surgery, population cohort). Endometriosis was diagnosed visually at laparoscopy/laparotomy or by pelvic magnetic resonance imaging in the operative and population cohorts, respectively. Logistic regression estimated the adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for each cohort.

RESULTS:

The incidence of visualized endometriosis was 40% in the operative cohort (11.8% stage 3-4 by revised criteria from the American Society for Reproductive Medicine), and 11% stage 3-4 in the population cohort by magnetic resonance imaging. An infertility history increased the odds of an endometriosis diagnosis in both the operative (AOR, 2.43; 95% CI, 1.57-3.76) and population (AOR, 7.91; 95% CI, 1.69-37.2) cohorts. In the operative cohort only, dysmenorrhea (AOR, 2.46; 95% CI, 1.28-4.72) and pelvic pain (AOR, 3.67; 95% CI, 2.44-5.50) increased the odds of diagnosis, while gravidity (AOR, 0.49; 95% CI, 0.32-0.75), parity (AOR, 0.42; 95% CI, 0.28-0.64), and body mass index (AOR, 0.95; 95% CI, 0.93-0.98) decreased the odds of diagnosis. In all sensitivity analyses for different diagnostic subgroups, infertility history remained a strong risk factor.

CONCLUSION:

An infertility history was a consistent risk factor for endometriosis in both the operative and population cohorts of the ENDO Study. Additionally, identified risk factors for endometriosis vary based upon cohort selection and diagnostic accuracy. Finally, endometriosis in the population may be more common than recognized.

 

 

 

Acta Med Iran. 2012;50(12):839-42.

Primary ovarian and pararectal hydatid cysts mimicking pelvic endometriosis.

Bozkurt M1Bozkurt DKÇil ASKaraman M.

 

Abstract

We report a case of 48-year-old woman with multiple hydatid cysts in pararectal region and right paraovarian localization with an unusual sonographic and computed tomographic presentation mimicking a pelvic endometriosis. During laparotomy, multiple pararectal and right ovarian cysts resembling endometriosis were resected. Pathologic examination gives the diagnosis of hydatid cysts. Retrospectively, we investigate the primary infection but the patient had no history of hepatic and liver involvement, it is a case of primary infection.

 

 

Nihon Hinyokika Gakkai Zasshi. 2013 Jan;104(1):30-2.

Uretero-fallopian fistula secondary to low anterior resection for rectal cancer.

Yokoyama H1Ishida KTate KFujita T.

 

Abstract

A 71-year-old woman presented with lower abdominal pain and urinary incontinence 18 days after low anterior resection for rectal cancer. Computed tomography and magnetic resonance urography revealed right hydronephrosis, cystic mass in the right pelvic cavity and hydrometra. Positron emission tomography showed dilated right upper urinary tract communicating with dilated right fallopian tube and uterine body, and the finding was quite characteristic. Laboratory studies revealed that the serum and the fluid from hydrometra levels of creatinine were 1.06 mg/dL and 6.15 mg/dL, respectively. We diagnosed this case as uretero-fallopian fistula. Since the conservative management of uretero-fallopian fistula with ureteral stent was not accomplished, she underwent right ureteroureterostomy and adnexectomy. The intraoperative findings included dilated right ureter and fallopian tube adherent to the stenotic right ureteral segment ligated by suture during prior surgery. The histopathological findings showed endometriosis and inflammatory changes of uterine appendages. Follow-up at 3 months demonstrated resolution of the urinary incontinence and the ureteral obstruction and fistula.

 

 

J Coll Physicians Surg Pak. 2013 Mar;23(3):190-3. doi: 03.2013/JCPSP.190193.

Diagnostic laparoscopic findings in chronic pelvic pain.

Baloch S1Khaskheli MNMalik AM.

 

Abstract

OBJECTIVE:

To assess the cause of pain on diagnostic laparoscopy in women with chronic pelvic pain and equivocal clinical and ultrasound examination.

STUDY DESIGN:

Cross-sectional observational study.

PLACE AND DURATION OF STUDY:

Red Crescent General Hospital, Hyderabad, Sindh, from January 2007 to December 2009.

METHODOLOGY:

All the women presenting with chronic pelvic pain for more than 6 months duration, without any obvious pathological findings on clinical as well as on ultrasound examination were recruited. Women with chronic pelvic pain and having pelvic pathological lesions detected on clinical and/or ultrasound examination were excluded. Clinical, ultrasound, and laparoscopic data was collected and analyzed on SPSS version 14. The results were described as frequency, proportion, compared by chi-square test with significance at p < 0.05.

RESULTS:

Highest frequency of chronic pelvic pain was observed in women aged between 26 – 35 years (62.4%), 53 out of 85 women. Most of these women were married (90.6%) and nulliparous (47.1%). Pain was reported as dull and sharp by 35 women (41.2%), infertility (n = 46, 54.1%) and dyspareunia (n = 45, 52.9%) were the commonest co-existent complaints. On laparoscopic examination, pathological lesions were detected in 65, tuberculosis in 17 (20%) endometriosis in 11 women (12.9%), pelvic inflammatory diseases and pelvic adhesion in 8 (9.4%) women each and ovarian cyst in 6 women (7.1%).

CONCLUSION:

Positive laparoscopic yield was high in women with pelvic pain. Pelvic tuberculosis was the most common pathology detected followed by endometriosis, pelvic inflammatory disease and adhesions.

 

 

 

 

Endocr Res. 2013;38(4):223-31. doi: 10.3109/07435800.2013.774011. Epub 2013 Mar 4.

The expression status of G protein-coupled receptor GPR30 is associated with the clinical characteristics of endometriosis.

Yuguchi H1Tanabe AHayashi ATanaka YOkuda KYamashita YTerai YOhmichi M.

 

Abstract

INTRODUCTION:

GPR30 is a seven-transmembrane G protein-coupled estrogen receptor that regulates endometrial cellular responses to estrogen. GPR30 is often highly expressed in cancer cells from aggressive tumors. The aim of this study was to evaluate the expression patterns of GPR30 in endometriosis during medical treatment.

PATIENTS:

A total of 38 females, 28 patients with endometriosis and 10 patients with leiomyoma who underwent laparoscopic surgery were included this study.

INTERVENTION:

Eutopic endometrial tissue sampling from women without endometriosis and ectopic endometrial tissue sampling from women with endometriosis.

MAIN OUTCOME MEASURE:

A quantitative real-time polymerase chain reaction analysis of the mRNA expression in eutopic and ectopic endometrial tissues with or without GnRH agonist treatment. The expression of GPR30 was confirmed by immunohistochemistry.

RESULTS:

There was an increased level of GPR30 mRNA in eutopic endometrium during the proliferative phase, whereas higher expression was observed in the ectopic endometrium during the secretory phase. Increased GPR30 mRNA was observed in ectopic endometrium in comparison to eutopic endometrium. GnRH agonist treatment before laparoscopic surgery decreased GPR30 mRNA in ectopic endometrium. The immunohistochemical analysis also revealed that GPR30 was strongly expressed in epithelial cells in ectopic endometrium, whereas GnRH agonist treatment decreased the GPR30 expression.

CONCLUSION:

High levels of GPR30 expression can play an important role in the progression of endometriosis.

 

 

 

 

Ann Saudi Med. 2013 Jan-Feb;33(1):34-9. doi: 10.5144/0256-4947.2013.34.

Fertility and pregnancy outcomes following resectoscopic septum division with and without intrauterine balloon stenting: a randomized pilot study.

Abu Rafea BF1Vilos GAOraif AMPower SGCains JHVilos AG.

 

Abstract

BACKGROUND AND OBJECTIVES:

Although uterine stenting is performed routinely following hysteroscopic metroplasty, we were unable to find any evidence documenting its value with regards to septum reformation and/or obstetrical performance. To evaluate the benefits of intrauterine Foley catheter/balloon splinting after resectoscopic septum division on septum reformation, fertility, and pregnancy outcomes.

DESIGN AND SETTING:

Prospective, randomized controlled pilot study (Canadian Task Force Classification I) conducted in university affiliated teaching hospital.

PATIENTS AND METHODS:

Twenty-eight women with infertility and/or adverse pregnancy outcomes diagnosed with intrauterine septum were randomized into having a No. 14 pediatric Foley catheter/balloon for 5 days (n=13) vs. no balloon (n=15) following resectoscopic septum division. None of the patients received preoperative endometrial thinning, antibiotic prophylaxis or adjuvant postoperative hormone therapy. All uterine septa were divided under general anaesthesia using a 26 F (9 mm) resectoscope with a monopolar electrical knife using glycine irrigant solution (1.5%) and 120 watts of power of low voltage (cut) waveform.

RESULTS:

The median age (range) was 29 years (23-38) and 32 years (22-40), respectively (P=.59). The groups were comparable by age, past obstetrical performance and comorbidities including endometriosis stage I-IV in 3 and 4 women, in the catheter/balloon and balloon group, respectively, and one in each group of polycystic ovarian syndrome and Crohn disease and one case of tubal obstruction in the balloon group. There were no intra- or postoperative complications. At 3 months, a hysterosalpingogram was done in 10 (77%) and 13 (87%) women, respectively, the results of which were normal. At 12-18 months, 1 woman in the balloon and 3 in the control group were not trying to conceive and 1 in each group had not conceived. Of the remaining women, 11 (92%) in each group had conceived and pregnancy outcomes included spontaneous abortion 3 (25%) and 4 (33.3%), ectopic pregnancy 0 and 1, second trimester loss 1 (8.3%) and 0 and term pregnancy 8 (66.6%) in both groups. Conception through assisted reproductive technology occurred in 2 and 1 woman, respectively.

CONCLUSIONS:

Following resectoscopic septum division with monopolar knife electrode, splinting the uterine cavity with Foley catheter provided no advantage in septum reformation, clinical pregnancy rate, and pregnancy outcomes.

 

 

J Cell Physiol. 2013 Sep;228(9):1927-34. doi: 10.1002/jcp.24358.

Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects.

Crispi S1Piccolo MTD’Avino ADonizetti AViceconte RSpyrou MCalogero RABaldi ASignorile PG.

 

Abstract

Endometriosis is a common benign pathology, characterised by the presence of endometrial tissue outside the endometrial cavity with a prevalence of 10-15% in reproductive-aged women. The pathogenesis is not completely understood, and several theories have been proposed to explain the aetiology. Our group has recently described the presence of ectopic endometrium in a consistent number of human female foetuses analysed by autopsy, reinforcing the hypothesis that endometriosis may be generated by defects during the organogenesis of the female reproductive trait. Herein, in order to identify, at molecular level, changes involved in the disease, we compared the transcriptional profiling of ectopic endometrium with the corresponding eutopic one. Statistical analyses lead us to identify some genes specifically deregulated in the ectopic endometrium, that are involved in gonad developmental process or in wound healing process. Among them, we identified BMP4 and GREM1. BMP4 was never associated before to endometriosis and is involved in the mesoderm-Müllerian duct differentiation. GREM1 is needed for the initial step of the ureter growth and perhaps could possibly be involved in Müller ducts differentiation. These molecules might be related to the endometriosis aetiology since we showed that their expression is not related to the menstrual cycle phase both at RNA and at protein levels. These data support the theory that embryological defects could be responsible of the endometriosis generation.

 

 

 

Fertil Steril. 2013 May;99(6):1705-13. doi: 10.1016/j.fertnstert.2013.01.133. Epub 2013 Feb 22.

Possible involvement of signal transducer and activator of transcription-3 in cell-cell interactions of peritoneal macrophages and endometrial stromal cells in human endometriosis.

Itoh F1Komohara YTakaishi KHonda RTashiro HKyo SKatabuchi HTakeya M.

 

Abstract

OBJECTIVE:

To investigate interactions between peritoneal macrophages and endometrial stromal cells (ESCs) involved in the development of endometriosis.

DESIGN:

Clinicopathologic and in vitro studies.

SETTING:

Department of Obstetrics and Gynecology and Department of Pathology, Kumamoto University Hospital.

PATIENT(S):

Women undergoing laparoscopy or laparotomy to treat endometriosis or other benign gynecologic conditions.

INTERVENTION(S):

We collected samples of peritoneal fluid (ascites), endometrium, and endometriotic tissues. We cocultured ESCs in vitro with or without human macrophages.

MAIN OUTCOME MEASURE(S):

Macrophage phenotypes in peritoneal fluid were determined via immunostaining. Proliferation of ESCs and activation of signal transducer and activator of transcription-3 (Stat3) in cocultures were evaluated.

RESULT(S):

The endometriosis group had a significantly higher total number of macrophages in ascites compared with the control group, but the ratios of CD163+ alternatively activated macrophages (M2) in the two groups did not differ significantly. Coculture with M2 macrophages significantly up-regulated ESC proliferation and Stat3 activation in ESCs in vitro. Proliferation of ESCs was suppressed after Stat3 was down-regulated by small interfering RNA. Stat3 was activated in epithelial cells and ESCs in human endometriotic lesions.

CONCLUSION(S):

Interactions between M2 macrophages and ESCs via Stat3 activation may play an important role in the development of endometriosis.

 

 

 

Gynecol Endocrinol. 2013 May;29(5):455-9. doi: 10.3109/09513590.2013.769516. Epub 2013 Mar 6

Elevated glycodelin-A concentrations in serum and peritoneal fluid of women with ovarian endometriosis.

Kocbek V1Vouk KMueller MDRižner TLBersinger NA.

 

Abstract

The aim of this study was to evaluate serum and peritoneal fluid (PF) glycodelin-A concentrations in women with ovarian endometriosis. Ninety-nine matched pairs of serum and PF samples were included in our study. The case group comprised 57 women with ovarian endometriosis and the control group 42 healthy women undergoing sterilization or patients with benign ovarian cysts. Glycodelin-A concentrations were measured using ELISA. Endometriosis patients had significantly higher serum and PF glycodelin-A concentrations compared to controls, and this increase was observed in both proliferative and secretory cycle phases. Glycodelin-A concentrations were more than 10-fold higher in PF than in serum and correlated with each other. Intensity and frequency of menstrual pain positively correlated with glycodelin-A concentrations. Sensitivity and specificity of glycodelin-A as a biomarker for ovarian endometriosis were 82.1% and 78.4% in serum, and 79.7% and 77.5% in PF, respectively. These results indicate that Glycodelin-A has a potential role as a biomarker to be used in combination with other, independent marker molecules.

 

 

 

Gynecol Obstet Fertil. 2014 Jan;42(1):20-6. doi: 10.1016/j.gyobfe.2012.09.013. Epub 2013 Feb 23.

Interest of laparoscopy in infertile couple with normal hysterosalpingography.

Fatnassi R1Kaabia O2Laadhari S3Briki R2Dimassi Z3Bibi M2Hidar S2Ben Regaya L2Khairi H2.

 

Abstract

OBJECTIVES:

The diagnostic laparoscopy has long been the key consideration in the export of female infertility. This place is being reconsidered, especially in the case of normal hysterosalpingogrophy (HSG), because of the advent of assisted reproductive technologies which are more efficient, and because of the improvement of medical imaging techniques which are more sensitive and specific. We wanted to clarify the place of the diagnostic laparoscopy in the balance of female infertility in normal HSG.

PATIENTS AND METHODS:

It is a retrospective study on a series of 100 observations of infertile patients with a normal HSG and having a diagnostic laparoscopy in the department of Gynecology and Obstetrics at Farhat Hached hospital in Sousse (Tunisia) from 1st January 1993 to 1st March 2003.

RESULTS:

The mean age was 32.3years; the mean duration of infertility was 70.47months. Laparoscopy revealed pelvic abnormalities in 45% of cases, dominated by disease tubo-adhesions (23%), endometriosis was found in 6% of cases. These anomalies are considered major in 23% of cases and minor in 22% of cases. Conducting a surgical procedure in the same operating time (adhesiolysis, tubal plastic surgery, electrocoagulation of endometriosis implants) could improve the prognosis of fertility. Only 20 patients were followed among the 45 with pelvic abnormalities, seven pregnancies have been completed (35% of cases).

DISCUSSION AND CONCLUSION:

Laparoscopy has improved the prognosis for the fertility of our patients by treating abnormalities involved in infertility. It is estimated that the prognosis can be improved by selecting patients with risk factors for pelvic abnormalities.

 

 

 

Hum Reprod. 2013 May;28(5):1280-8. doi: 10.1093/humrep/det017. Epub 2013 Mar 5.

External validation of the endometriosis fertility index (EFI) staging system for predicting non-ART pregnancy after endometriosis surgery.

Tomassetti C1Geysenbergh BMeuleman CTimmerman DFieuws SD’Hooghe T.

 

Abstract

STUDY QUESTION:

Can the ability of the endometriosis fertility index (EFI) to predict non-assisted reproductive technology (ART) pregnancy after endometriosis surgery be confirmed by an external validation study?

SUMMARY ANSWER:

The significant relationship between the EFI score and the time to non-ART pregnancy observed in our study represents an external validation of this scoring system.

WHAT IS KNOWN AND WHAT THIS PAPER ADDS:

The EFI was previously developed and tested prospectively in a single center, but up to now no external validation has been published. Our data provide validation of the EFI in an external fertility unit on a robust scientific basis, to identify couples with a good prognosis for spontaneous conception who can therefore defer ART treatment, regardless of their revised American Fertility Society (rAFS) endometriosis staging.

DESIGN:

Retrospective cohort study where the EFI was calculated based on history and detailed surgical findings, and related to pregnancy outcome in 233 women attempting non-ART conception immediately after surgery; all data used for EFI calculation and analysis of reproductive outcome had been collected prospectively as part of another study.

PARTICIPANTS AND SETTING:

The EFI score was calculated (score 0-10) for 233 women with all rAFS endometriosis stages (minimal-mild, n = 75; moderate-severe, n = 158) after endometriosis surgery (1 September 2006-30 September 2010) in a university hospital-based reproductive medicine unit with combined expertise in reproductive surgery and medically assisted reproduction. All participants attempted non-ART conception immediately after surgery by natural intercourse, ovulation induction with timed intercourse or intrauterine insemination (with or without ovulation induction or controlled ovarian stimulation).

DATA ANALYSIS METHOD:

All analyses were performed for three different definitions of pregnancy [overall (any HCG >25 IU/l), clinical and ongoing >20 weeks]. Six groups were distinguished (EFI scores 1-3, 4, 5, 6, 7+8, 9+10), and Kaplan-Meier (K-M) estimates for cumulative pregnancy rate were calculated. Subjects were censored when they were lost to follow-up, had subsequent surgery for endometriosis, started ovarian suppression or underwent ART. As K-M estimates might overestimate the actual event rate, cumulative incidence estimates treating ART as competing event were also calculated. Cox regression analysis was used to assess the performance of EFI and constituting variables. Performance of the score (prediction, discrimination) was quantified with the following methods: mean squared error of prediction (Brier score), areas under the receiver-operating curve and global concordance index C(τ).

MAIN RESULTS AND THE ROLE OF CHANCE:

There was a highly significant relationship between the EFI and the time to non-ART pregnancy (cumulative overall pregnancy rate, P = 0.0004), with the K-M estimate of cumulative overall pregnancy rate at 12 months after surgery equal to 45.5% [95% confidence interval (CI) 39.47-49.87]-ranging from 16.67% (95% CI 5.01-47.65) for EFI scores 0-3, to 62.55% (95% CI 55.18-69.94) for EFI scores 9-10. For each increase of 1 point in the EFI score, the relative risk of becoming pregnant increased by 31% (95% CI 16-47%; i.e. hazard ratio 1.31). The ‘least function score’-which assesses the tubal/ovarian function at conclusion of surgery-was found to be the most important contributor to the total EFI score among all the other variables (age, duration of infertility, prior pregnancy, AFS endometriosis lesion and total score).

BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION:

The EFI score had a moderate performance in the prediction of the pregnancy rate. Indeed, the decrease in prediction error was rather small, as shown by the decrease in Brier score from 0.213 to 0.198, and low estimates for R&sup2; (13%) and C(τ) (0.629).

GENERALIZABILITY TO OTHER POPULATIONS:

As the EFI was validated externally in our own European population after initial testing by Adamson and Pasta (Endometriosis fertility index: the new, validated endometriosis staging system. Fertil Steril 2010;94:1609-1615) in an American population, it appears that the EFI can be used clinically to counsel infertile endometriosis patients receiving reproductive surgery in specialized centers about their post-operative conception options.

STUDY FUNDING/COMPETING INTEREST(S):

This research was supported by funds obtained via the Clinical Research Fund of the University Hospitals Leuven, Belgium, via the Ferring Chair in Reproductive Medicine and Surgery, and the Serono Chair in Reproductive Medicine granted to the Leuven University Fertility Center. The authors have no conflicts of interest to declare.

 

 

 

Cancer Epidemiol Biomarkers Prev. 2013 May;22(5):880-90. doi: 10.1158/1055-9965.EPI-12-1030-T. Epub 2013 Mar 5.

Combined and interactive effects of environmental and GWAS-identified risk factors in ovarian cancer.

Pearce CL1Rossing MALee AWNess RBWebb PMfor Australian Cancer Study (Ovarian Cancer)Australian Ovarian Cancer Study GroupChenevix-Trench GJordan SMStram DAChang-Claude JHein RNickels SLurie GThompson PJCarney MEGoodman MTMoysich KHogdall EJensen AGoode ELFridley BLCunningham JMVierkant RAWeber RPZiogas AAnton-Culver HGayther SAGentry-Maharaj AMenon URamus SJBrinton LWentzensen NLissowska JGarcia-Closas MMassuger LFKiemeney LAVan Altena AMAben KKBerchuck ADoherty JAIversen EMcGuire VMoorman PGPharoah PPike MCRisch HSieh WStram DOTerry KLWhittemore AWu AHSchildkraut JMKjaer SKOvarian Cancer Association Consortium.

 

Abstract

BACKGROUND:

There are several well-established environmental risk factors for ovarian cancer, and recent genome-wide association studies have also identified six variants that influence disease risk. However, the interplay between such risk factors and susceptibility loci has not been studied.

METHODS:

Data from 14 ovarian cancer case-control studies were pooled, and stratified analyses by each environmental risk factor with tests for heterogeneity were conducted to determine the presence of interactions for all histologic subtypes. A genetic “risk score” was created to consider the effects of all six variants simultaneously. A multivariate model was fit to examine the association between all environmental risk factors and genetic risk score on ovarian cancer risk.

RESULTS:

Among 7,374 controls and 5,566 cases, there was no statistical evidence of interaction between the six SNPs or genetic risk score and the environmental risk factors on ovarian cancer risk. In a main effects model, women in the highest genetic risk score quartile had a 65% increased risk of ovarian cancer compared with women in the lowest [95% confidence interval (CI), 1.48-1.84]. Analyses by histologic subtype yielded risk differences across subtype for endometriosis (Phet < 0.001), parity (Phet < 0.01), and tubal ligation (Phet = 0.041).

CONCLUSIONS:

The lack of interactions suggests that a multiplicative model is the best fit for these data. Under such a model, we provide a robust estimate of the effect of each risk factor that sets the stage for absolute risk prediction modeling that considers both environmental and genetic risk factors. Further research into the observed differences in risk across histologic subtype is warranted.

 

 

 

Fertil Steril. 2013 May;99(6):1695-704. doi: 10.1016/j.fertnstert.2013.01.131. Epub 2013 Mar 7.

Postoperative digestive function after radical versus conservative surgical philosophy for deep endometriosis infiltrating the rectum.

Roman H1Vassilieff MTuech JJHuet ESavoye GMarpeau LPuscasiu L.

 

Abstract

OBJECTIVE:

To compare delayed digestive outcomes in women managed by two different surgical philosophies: a radical approach mainly related to colorectal resection, and a conservative approach involving rectal shaving and rectal nodule excision.

DESIGN:

“Before and after” comparative retrospective study.

SETTING:

University tertiary referral center.

PATIENT(S):

Seventy-five patients managed by surgery for deep endometriosis infiltrating the rectum.

INTERVENTION(S):

Twenty-four women were managed during a period when surgeons pursued a radical philosophy toward treatment, and 51 women were managed during a period when a conservative philosophy was adopted.

MAIN OUTCOMES MEASURE(S):

Standardized gastrointestinal questionnaires: the Gastrointestinal Quality of Life Index, the Knowles-Eccersley-Scott Symptom Questionnaire, the Bristol Stool Score, and the Fecal Incontinence Quality of Life Score.

RESULT(S):

Preoperative patient characteristics, rectal nodule features, and associated localizations of the disease were comparable between the two groups. During the radical period, colorectal resection was carried out in 67% of patients, whereas during the second period only 20% of women underwent colorectal resection. Women managed according to the conservative philosophy had significantly improved results on the Knowles-Eccersley-Scott Symptom Questionnaire, Gastrointestinal Quality of Life Index, and depression/self-perception Fecal Incontinence Quality of Life Score, and significantly improved values for various items related to postoperative constipation: unsuccessful evacuatory attempts, feeling incomplete evacuation, abdominal pain, time taken to evacuate, difficulty evacuating causing a painful effort, and stool consistency.

CONCLUSION(S):

It seems that reducing the rate of colorectal resection leads to better functional outcomes in women presenting with rectal endometriosis, lending support to the conservative surgical philosophy over mandatory colorectal resection.

 

 

 

Int J Gynaecol Obstet. 2013 May;121(2):173-5. doi: 10.1016/j.ijgo.2012.11.023. Epub 2013 Mar 1.

Clinical characteristics of 70 patients with Herlyn-Werner-Wunderlich syndrome.

Tong J1Zhu LLang J.

 

Abstract

OBJECTIVE:

To analyze the clinical characteristics of patients with Herlyn-Werner-Wunderlich (HWW) syndrome.

METHODS:

Seventy patients with a confirmed diagnosis of HWW syndrome admitted to the Peking Union Medical College Hospital between January 1995 and December 2010 were retrospectively reviewed, and long-term follow-up data were analyzed.

RESULTS:

The lateral distribution of hemivaginal obstruction and renal agenesis favored the right side in 42 patients (60.0%). Age at onset of symptoms was significantly different between patients with complete and those with incomplete hemivaginal obstruction (12.86 ± 1.84 vs 20.68 ± 7.43 years; P<0.05). The primary gynecologic complaint was dysmenorrhea, which occurred in 45 (64.3%) patients. Endometriosis was observed in 12 (17.1%) patients, and 14 (20.0%) patients with hemivaginal obstruction had acute pelvic inflammation history. All patients underwent vaginal septectomy. There were 52 pregnancies among 28 (84.8%) of the 33 women who wished to conceive.

CONCLUSION:

The clinical presentation of patients with HWW syndrome was significantly different between those with complete and those with incomplete hemivaginal obstruction. Full resection of the vaginal septum resulted in good outcomes.

 

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(1):80-3. doi: 10.1016/j.ejogrb.2013.01.024. Epub 2013 Mar 7.

Determination of cathepsins B, D and G concentration in eutopic proliferative endometrium of women with endometriosis by the surface plasmon resonance imaging (SPRI) technique.

Laudanski P1Gorodkiewicz ERamotowska BCharkiewicz RKuzmicki MSzamatowicz J.

 

Abstract

OBJECTIVE:

To determine the concentrations of cathepsins B, D and G in proliferative eutopic endometrium of patients with and without endometriosis, by use of the surface plasmon resonance imaging (SPRI) technique.

STUDY DESIGN:

A total of 55 patients were recruited in the study: 31 patients with endometriosis (stages I-IV) and 24 controls. Endometrial samples were obtained in the first phase of the menstrual cycle from regularly menstruating premenopausal women, prior to laparoscopy, by the use of aspiration biopsy. Endometriosis was appropriately classified according to the Revised American Fertility Society classification and confirmed by histopathology in every case. The SPRI technique was used to determine the concentration of cathepsins B, D and G. To compare the two groups for quantitative data, Mann-Whitney-Wilcoxon’s test was used due to the non-normal distribution of the tested variables and normality of distribution was assessed using Shapiro-Wilk W test.

RESULTS:

The concentration of the three examined cathepsins was higher in the proliferative eutopic endometrium of patients with endometriosis, especially in advanced stages, e.g. III and IV, when compared to healthy individuals. Corresponding median values were, for cathepsin B: [7.93 pmol/mg (min-max 2.82-15.71) vs 1.2 pmol/mg (min-max 0.7-15.49) p=0.0014], for cathepsin D: [1.86 pmol/mg (min-max 0.51-5.4) vs 1.03 pmol/mg (min-max 0.4-2.72) p=0.00041] and for cathepsin G: [0.6 pmol/mg (min-max 0.33-2.51) vs 0.3 pmol/mg (min-max 0.16-1.29) p=0.00051].

CONCLUSIONS:

Increased concentrations of cathepsins B, D and G in the proliferative eutopic endometrium may play a role in the implantation of endometrial tissue outside the uterine cavity.

 

 

 

Hum Reprod. 2013 Jun;28(6):1626-34. doi: 10.1093/humrep/det027. Epub 2013 Mar 6.

A physiological approach for treating endometriosis by recombinant pigment epithelium-derived factor (PEDF).

Chuderland D1Hasky NBen-Ami IKaplan-Kraicer RGrossman HShalgi R.

 

Abstract

STUDY QUESTION:

Is pigment epithelium-derived factor (PEDF) expressed in the rodent endometrium and can it be utilized to treat endometriosis without negatively affecting reproductive parameters?

SUMMARY ANSWER:

PEDF is dynamically expressed in rat endometrium throughout the estrous cycle in a reciprocal manner to vascular endothelial growth factor (VEGF); it possesses potent therapeutic properties for endometriosis that do not compromise the reproductive parameters.

WHAT IS KNOWN ALREADY:

Endometriosis pathogenesis depends mainly on neovascularization, with a high local level of VEGF. PEDF, a 50 kDa secreted glycoprotein with a potent anti-angiogenic activity, negates several strong pro-angiogenic factors, such as VEGF.

STUDY DESIGN, SIZE, DURATION:

Rat endometrial samples were collected at various days of the estrous cycle (n = 5 rats/day) and mRNA of VEGF and PEDF was determined. Endometriosis was induced by transplanting uterine pieces onto the inner surface of the abdominal wall of recipient rats, resulting in proliferation of the endometrial transplants. Recipient rats were randomly injected intravenously (IV), every third day for the next 3 weeks, with either Tris (‘control’; n = 7) or recombinant PEDF (rPEDF; 2 mg/kg/day; ‘PEDF prevention’; n = 7), while others were IV injected every third day starting from Day 9 after grafting until the end of 3 weeks, with rPEDF (2 mg/kg/day; ‘PEDF treatment’; n = 6). The effect of rPEDF on the duration of the estrous cycle and on the number of ovulated oocytes was evaluated in rats that were randomly divided into four groups and were injected with either Tris or rPEDF every third day for 3 weeks: naive rats (n = 6); rPEDF-treated rats (n = 5); endometriosis-induced rats (n = 5); or endometriosis + rPEDF rats (n = 6).

MATERIALS, SETTING, METHODS:

Reproductive parameters: the estrous cycle was evaluated by daily vaginal smears, and the number of ovulated oocytes in the oviductal ampullae of estrus rats was counted. The efficiency of endometriosis induction and treatment was evaluated on the third week after endometrial transplantation, on the day of pro-estrus. Endometrial transplants were isolated and weighted. PEDF and VEGF were monitored by quantitative PCR and immunohistochemistry using confocal microscopy.

MAIN RESULTS AND THE ROLE OF CHANCE:

PEDF mRNA and protein were dynamically expressed in the endometrium all throughout the estrous cycle, reciprocally to VEGF; VEGF was highly expressed during estrus while PEDF expression was low, and vice versa at metestrus II. The weight of the endometrial transplants was significantly reduced after PEDF administration (13% of control for ‘PEDF treatment’ rats; 7% of control for ‘PEDF prevention’ rats; P < 0.001). Histology of the transplants’ remnants showed a complete loss of their endometrial characteristics. Furthermore, the level of VEGF mRNA in the transplants of PEDF-administered rats was significantly lower (P < 0.05) than in transplants of control rats. Administration of rPEDF had no effect on the estrous cycle or ovulation rate of naive rats, while it had a significantly beneficial effect on the low ovulation rate of endometriosis-induced rats (P < 0.05).

LIMITATIONS, REASONS FOR CAUTION:

The experiments were performed in a rat model.

WIDER IMPLICATIONS OF THE FINDINGS:

The endometriosis therapeutic potency of PEDF that is exerted reciprocally to VEGF and does not compromise reproductive parameters offers a rational for using PEDF as a treatment for endometriosis with a potential of treating other reproductive angiogenic-related pathologies.

 

 

 

Int J Mol Sci. 2013 Mar 6;14(3):5367-79. doi: 10.3390/ijms14035367.

Endometriosis-associated ovarian cancer: a review of pathogenesis.

Worley MJ1Welch WRBerkowitz RSNg SW.

 

Abstract

Endometriosis is classically defined as the presence of endometrial glands and stroma outside of the endometrial lining and uterine musculature. With an estimated frequency of 5%-10% among women of reproductive age, endometriosis is a common gynecologic disorder. While in itself a benign lesion, endometriosis shares several characteristics with invasive cancer, has been shown to undergo malignant transformation, and has been associated with an increased risk of epithelial ovarian carcinoma (EOC). Numerous epidemiologic studies have shown an increased risk of EOC among women with endometriosis. This is particularly true for women with endometrioid and clear cell ovarian carcinoma. However, the carcinogenic pathways by which endometriosisassociated ovarian carcinoma (EAOC) develops remain poorly understood. Current molecular studies have sought to link endometriosis with EAOC through pathways related to oxidative stress, inflammation and hyperestrogenism. In addition, numerous studies have sought to identify an intermediary lesion between endometriosis and EAOC that may allow for the identification of endometriosis at greatest risk for malignant transformation or for the prevention of malignant transformation of this common gynecologic disorder. The objective of the current article is to review the current data regarding the molecular events associated with EAOC development from endometriosis, with a primary focus on malignancies of the endometrioid and clear cell histologic sub-types.

 

 

 

PLoS One. 2013;8(3):e57724. doi: 10.1371/journal.pone.0057724. Epub 2013 Mar 4.

Met is the most frequently amplified gene in endometriosis-associated ovarian clear cell adenocarcinoma and correlates with worsened prognosis.

Yamashita Y1Akatsuka SShinjo KYatabe YKobayashi HSeko HKajiyama HKikkawa FTakahashi TToyokuni S.

 

Abstract

Clear cell adenocarcinoma of the ovary (OCC) is a chemo-resistant tumor with a relatively poor prognosis and is frequently associated with endometriosis. Although it is assumed that oxidative stress plays some role in the malignant transformation of this tumor, the characteristic molecular events leading to carcinogenesis remain unknown. In this study, an array-based comparative genomic hybridization (CGH) analysis revealed Met gene amplification in 4/13 OCC primary tumors and 2/8 OCC cell lines. Amplification of the AKT2 gene, which is a downstream component of the Met/PI3K signaling pathway, was also observed in 5/21 samples by array-based CGH analysis. In one patient, both the Met and AKT2 genes were amplified. These findings were confirmed using fluorescence in situ hybridization, real-time quantitative PCR, immunoblotting, and immunohistochemistry. In total, 73 OCC cases were evaluated using real-time quantitative PCR; 37.0% demonstrated Met gene amplification (>4 copies), and 8.2% had AKT2 amplification. Furthermore, stage 1 and 2 patients with Met gene amplification had significantly worse survival than patients without Met gene amplification (p<0.05). Met knockdown by shRNA resulted in reduced viability of OCC cells with Met amplification due to increased apoptosis and cellular senescence, suggesting that the Met signaling pathway plays an important role in OCC carcinogenesis. Thus, we believe that targeted inhibition of the Met pathway may be a promising treatment for OCC.

 

 

 

J Nippon Med Sch. 2013;80(1):78-82.

Mimic mini-laparoscopic surgery is a simple and secure approach using direct placement of 3-mm trocars without noticeable scars.

Ichikawa M1Akira SHamano EOno SMine KTakeshita T.

 

Abstract

Minimally invasive surgery is widely used in gynecology. Women who seek a cosmetic advantage (i.e., concealed scars) choose minimally invasive surgery. Although laparoendoscopic single-site surgery could be an ideal solution, some of our patients have had cosmetic problems, such as pigmentation and cicatrix of the umbilicus. In addition, umbilical eversion and umbilical herniation occasionally develop. Therefore, mini-laparoscopic surgery using 3-mm trocars can be recommended for patients who do not want the natural appearance of the navel to be altered. We have developed an approach to achieve a superior cosmetic outcome by direct placement of 3-mm trocars in the lateral wall of the abdomen and at the lower border of the pubic hair. We refer to this method as mimic mini-laparoscopic surgery and report cases in which this procedure was used.

 

 

PLoS One. 2013;8(3):e58257. doi: 10.1371/journal.pone.0058257. Epub 2013 Mar 5.

Genome-wide association study link novel loci to endometriosis.

Albertsen HM1Chettier RFarrington PWard K.

 

Abstract

Endometriosis is a common gynecological condition with complex etiology defined by the presence of endometrial glands and stroma outside the womb. Endometriosis is a common cause of both cyclic and chronic pelvic pain, reduced fertility, and reduced quality-of-life. Diagnosis and treatment of endometriosis is, on average, delayed by 7-10 years from the onset of symptoms. Absence of a timely and non-invasive diagnostic tool is presently the greatest barrier to the identification and treatment of endometriosis. Twin and family studies have documented an increased relative risk in families. To identify genetic factors that contribute to endometriosis we conducted a two-stage genome-wide association study (GWAS) of a European cohort including 2,019 surgically confirmed endometriosis cases and 14,471 controls. Three of the SNPs we identify associated at P<5×10(-8) in our combined analysis belong to two loci: LINC00339-WNT4 on 1p36.12 (rs2235529; P = 8.65×10(-9), OR = 1.29, CI = 1.18-1.40) and RND3-RBM43 on 2q23.3 (rs1519761; P = 4.70×10(-8), OR = 1.20, Cl = 1.13-1.29, and rs6757804; P = 4.05×10(-8), OR = 1.20, Cl = 1.13-1.29). Using an adjusted Bonferoni significance threshold of 4.51×10(-7) we identify two additional loci in our meta-analysis that associate with endometriosis:, RNF144B-ID4 on 6p22.3 (rs6907340; P = 2.19×10(-7), OR = 1.20, Cl = 1.12-1.28), and HNRNPA3P1-LOC100130539 on 10q11.21 (rs10508881; P = 4.08×10(-7), OR = 1.19, Cl = 1.11-1.27). Consistent with previously suggested associations to WNT4 our study implicate a 150 kb region around WNT4 that also include LINC00339 and CDC42. A univariate analysis of documented infertility, age at menarche, and family history did not show allelic association with these SNP markers. Clinical data from patients in our study reveal an average delay in diagnosis of 8.4 years and confirm a strong correlation between endometriosis severity and infertility (n = 1182, P<0.001, OR = 2.18). This GWAS of endometriosis was conducted with high diagnostic certainty in cases, and with stringent handling of population substructure. Our findings broaden the understanding of the genetic factors that play a role in endometriosis.

 

 

Fertil Steril. 2013 Jun;99(7):1965-73.e2. doi: 10.1016/j.fertnstert.2013.01.146. Epub 2013 Mar 6.

Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4).

Gori I1Rodriguez YPellegrini CAchtari CHornung DChardonnens EWunder DFiche MCanny GO.

 

Abstract

OBJECTIVE:

To compare the expression of the prostaglandin (PG) E(2) transporter multidrug resistance-associated protein 4 (MRP4) in eutopic and ectopic endometrial tissue from endometriosis patients with that of control subjects and to examine whether MRP4 is regulated by the antiinflammatory lipid lipoxin A(4) (LXA(4)) in endometriotic epithelial cells.

DESIGN:

Molecular analysis in human samples and a cell line.

SETTING:

Two university hospitals and a private clinic.

PATIENT(S):

A total of 59 endometriosis patients and 32 age- and body mass index-matched control subjects undergoing laparoscopy or hysterectomy.

INTERVENTION(S):

Normal, eutopic, and ectopic endometrial biopsies as well as peritoneal fluid were obtained during surgery performed during the proliferative phase of the menstrual cycle. 12Z endometriotic epithelial cells were used for in vitro mechanistic studies.

MAIN OUTCOME MEASURE(S):

Tissue MRP4 mRNA levels were quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and localization was analyzed with the use of immunohistochemistry. Cellular MRP4 mRNA and protein were quantified by qRT-PCR and Western blot, respectively. PGE(2) was measured in peritoneal fluid and cell supernatants using an enzyme immunoassay (EIA).

RESULT(S):

MRP4 was expressed in eutopic and ectopic endometrium, where it was overexpressed in peritoneal lesions and localized in the cytoplasm of glandular epithelial cells. LXA(4) attenuated MRP4 mRNA and protein levels in endometriotic epithelial cells in a dose-dependent manner, while not affecting the expression of enzymes involved in PGE(2) metabolism. Investigations employing receptor antagonists and small interfering RNA revealed that this occurred through estrogen receptor α. Accordingly, LXA(4) treatment inhibited extracellular PGE(2) release.

CONCLUSION(S):

We report for the first time that MRP4 is expressed in human endometrium, elevated in peritoneal endometriosis, and modulated by LXA(4) in endometriotic epithelial cells.

 

 

 

 

Fertil Steril. 2013 Jun;99(7):1974-9. doi: 10.1016/j.fertnstert.2013.02.002. Epub 2013 Mar 7.

The oncofetal protein IMP3: a novel biomarker and triage tool for premalignant atypical endometriotic lesions.

Vercellini P1Cribiù FMDel Gobbo ACarcangiu MLSomigliana EBòsari S.

 

Abstract

OBJECTIVE:

To determine whether the oncofetal protein IMP3 is detectable in endometriomas with or without histological atypia and whether IMP3 staining can be used as a triage tool to identify foci of atypical endometriosisin doubtful cases.

DESIGN:

Retrospective study.

SETTING:

Academic department and referral center for endometriosis.

PATIENT(S):

A consecutive series of 516 women who underwent excision of 874 endometriomas.

INTERVENTION(S):

Histological review by three expert pathologists and immunohistochemical staining for IMP3.

MAIN OUTCOME MEASURE(S):

Test performance of IMP3 immunohistochemistry versus first-round histology.

RESULT(S):

The prevalence of atypical endometriosis was 1.7% (95% confidence interval [CI], 0.9%-3.3%) based on the number of women and 1.0% (95% CI, 0.5%-1.9%) based on the number of cysts. Three cases of atypical endometriosis were identified at first-round histological examination. Immunohistochemistry detected seven of the eight cases diagnosed as preneoplastic atypia at second-round histology and one case diagnosed as reactive atypia at second-round histology. The sensitivity of first-round histology was 33.3%, compared with 88.9% of IMP3 immunohistochemistry.

CONCLUSION(S):

Immunohistochemical staining for IMP3 expression is a simple, inexpensive, and sensitive test that can be used in routine clinical practice as a triage tool to discriminate between cytological/structural atypia and confounding benign conditions.

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(1):103-7. doi: 10.1016/j.ejogrb.2013.02.010. Epub 2013 Mar 7.

Peritoneal fluid concentrations of β-chemokines in endometriosis.

Margari KM1Zafiropoulos AHatzidaki EGiannakopoulou CArici AMatalliotakis I.

 

Abstract

OBJECTIVE:

To examine whether the levels of MCP-1, RANTES and MCP-3 in the peritoneal fluid correlate with endometriosis.

STUDY DESIGN:

Patients with endometriosis were compared with controls.

SETTING:

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.

SUBJECTS:

This study involved 95 women of reproductive age who were undergoing laparoscopy for evaluation of infertility or for pelvic pain. They were divided into an endometriosis group (n=54) and a control group (n=41).

INTERVENTIONS:

Peritoneal fluid samples were obtained and β-chemokines (MCP-1, RANTES and MCP-3) were measured using ELISA.

STATISTICAL ANALYSIS:

Mean and median values were used to present values. Due to the non-normality of chemokines, a log transformation was applied. Differences were examined using independent samples t-test. One-way ANOVA and Tukey HSD multiple comparison post hoc tests were applied. A significance level at 0.05 was set.

RESULTS:

The levels of MCP-1 are higher (p for log values=0.024) in the control group (mean=687.6, SD=467.7 pg/ml) than those of the endometriosis group (mean=570.4, SD=633.1 pg/ml). The same is true for the median values of MCP-1 (control median=568.5, endometriosis median=384.7 pg/ml). MCP-3 and RANTES do not differ significantly (MCP-3 p=0.787, RANTES p=0.153). The levels of MCP-1 in patients with stage II endometriosis are significantly lower in comparison with stage III (p=0.048) and stage IV (p=0.033) endometriosis.

CONCLUSIONS:

A decrease in the concentrations of MCP-1 in stage I endometriosis has been observed, which is even larger in stage II, in contrast to stage III and stage IV endometriosis, which exhibit concentrations similar to the controls.

 

 

 

Am J Dermatopathol. 2013 Dec;35(8):856-8. doi: 10.1097/DAD.0b013e3182858460.

Multilocular mesothelial proliferation involving the skin of the umbilicus.

Konstantinova AM1Michal MKacerovska DKazakov DV.

 

Abstract

Multilocular mesothelial proliferation (MMP) is a rare lesion that mainly arises from the peritoneal mesothelium. Most often, it occurs in women of reproductive age, with a history of abdominal surgery, endometriosis, or pelvic inflammatory disease. We describe an unusual case of a 73-year-old woman affected by a large MMP, which involved the skin and presented clinically as a cutaneous mass. To the best of our knowledge, MMP involving the umbilicus has never been reported in a peer-reviewed literature.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(1):93-8. doi: 10.1016/j.ejogrb.2013.02.007. Epub 2013 Mar 9.

Location-dependent value of pelvic MRI in the preoperative diagnosis of endometriosis.

Krüger K1Behrendt KNiedobitek-Kreuter GKoltermann KEbert AD.

 

Abstract

OBJECTIVES:

To investigate the value of magnetic resonance imaging (MRI) in the preoperative diagnosis of specific anatomical locations of endometriosis.

STUDY DESIGN:

Between July 2008 and April 2011, 152 women (mean age 33.5 ± 6.1 years) with clinical and sonographic suspicion of endometriosis underwent pelvic MRI using T2 and unenhanced T1 sequences with and without fat saturation. Two radiologists interpreted the following regions by consensus according to a standardized protocol: ovaries, vagina, pouch of Douglas, rectosigmoid colon, uterosacral ligament (USL), bladder, peritoneum, and other pelvic regions. The results of MRI were retrospectively correlated with the laparoscopic and histopathologic findings. The main outcome parameters, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (LR+) and the negative likelihood ratio (LR-), were determined.

RESULTS:

Sensitivity, specificity, PPV, NPV, accuracy, positive and the negative likelihood ratio were 87.6%, 84.6%, 94.3%, 70.2%, 86.8%, 5.69 and 0.15 for the pouch of Douglas (vagina: 81.4%, 81.7%, 79.2%, 83.8%, 81.6%, 4.45, 0.23; rectosigmoid colon: 80.2%, 77.5%, 80.2%, 77.5%, 78.9%, 3.56, 0.25; USL: 77.5%, 68.2%, 77.5%, 68.2%, 73.7%, 2.44, 0.33; ovaries: 86.3%, 73.6%, 78.4%, 82.8%, 80.3%, 3.27, 0.19; urinary bladder: 81.0%, 94.7%, 70.8%, 96.9%, 92.8%, 15.15, 0.20; peritoneum: 35.3%, 88.1%, 60.0%, 73.0%, 70.4%, 2.97, 0.73). All endometriotic implants at other localization were detected (abdominal wall in 4, groin in one patient).

CONCLUSIONS:

The value of MRI in preoperative diagnosis of endometriosis is dependent on the location of endometriosis. The highest accuracy was found in bladder endometriosis and the lowest in peritoneal endometriosis.

 

 

 

 

 

Pathology. 2013 Apr;45(3):229-42. doi: 10.1097/PAT.0b013e32835f2264.

Precursors and pathogenesis of ovarian carcinoma.

Lim D1Oliva E.

 

Abstract

The ultimate goal of defining cancer specific precursors is to facilitate early detection and intervention before the development of invasive malignancy. Unlike other malignancies involving the female genital tract such as cervical or endometrial carcinomas, precursor lesions of ovarian carcinomas have not been well characterised, resulting in a failure to develop effective screening programs. Recent clinicopathological and molecular studies have provided new insight into the origin and pathogenesis of ovarian carcinomas. It has been shown that ovarian cancer is comprised of different tumour types differing not only in morphology, but also in pathogenesis, molecular alterations and clinical progression. A dualistic model of ovarian carcinogenesis has been proposed. Type I tumours which include low grade serous, low grade endometrioid, clear cell, mucinous carcinomas and Brenner tumours, are generally indolent and tend to be genetically stable, although clear cell carcinoma would probably belong to an intermediate category. They demonstrate a step-wise progression from a benign precursor such as a benign to borderline tumour or endometriosis and are characterised by genetic aberrations targeting specific cell signalling pathways. Type II tumours comprise high grade serous, high grade endometrioid, and undifferentiated carcinomas as well as malignant mixed mesodermal tumours. They are clinically aggressive and exhibit high genetic instability with frequent p53 mutations. Mounting evidence suggests that many high grade serous carcinomas originate from the epithelium of the distal fallopian tube, and that serous tubal intraepithelial carcinoma (STIC) represents the putative precursor of these neoplasms. Low grade serous carcinomas arise via transformation of benign and borderline serous tumours, thought to be derived from inclusion cysts originating from the ovarian surface or tubal epithelium. Recently it has been suggested that papillary tubal hyperplasia may be a putative precursor lesion for serous borderline tumours. Both endometrioid and clear cell carcinomas develop from endometriosis, via alterations affecting different genetic pathways. The origin of mucinous and transitional cell neoplasms is not well characterised, although new data suggest a possible origin from transitional cell nests present at the tubal-mesothelial junction. Likewise, the pathogenesis of carcinosarcomas is also not well established because of their rarity but there is accumulating evidence that the carcinomatous component determines the course of the disease and gives rise to the malignant mesenchymal component. This review discusses recent developments in the pathogenesis of ovarian carcinoma, with particular emphasis on the putative precursor lesions that give rise to the major histological subtypes. Recognition of these lesions is not only important in improving the understanding of ovarian carcinogenesis, but it will also influence our approach to prevent, detect and treat these tumours.

 

 

 

Congenit Anom (Kyoto). 2013 Mar;53(1):9-17. doi: 10.1111/j.1741-4520.2012.00383.x.

Exposure to ethinyl estradiol prenatally and/or after sexual maturity induces endometriotic and precancerous lesions in uteri and ovaries of mice.

Koike E1Yasuda YShiota MShimaoka MTsuritani MKonishi HYamasaki HOkumoto KHoshiai H.

 

Abstract

Unrecognizable exposure to estrogenic substance may cause estrogen-dependent diseases, endometriosis and cancer. Pregnant mice (ICR/Jcl, CLEA) were exposed to 0.01 mg ethinyl estradiol (EE2 )/kg per day or vehicle (olive oil) through oral intubation from day 11 to 17 of gestation. They delivered their offspring and raised them. When the experimental female F1 mice were at 8 weeks of age, they were not exposed to EE2 or to the same dose of EE2 or to vehicle twice a week until 20 weeks of age. The control female F1 mice were exposed to the same dose of EE2 or vehicle alone, similarly. All mice were killed at 28 weeks of age. The resected uteri and ovaries were processed for microscopic examinations and for determination of the aromatase mRNA levels and aromatase protein through quantitative RT-PCR and Western blotting, respectively. Adenomyosis and adenocarcinomatous changes were significantly discernible in the EE2 -exposed uteri, and incidence of ectopic glands and serous cysts were significantly increased in the prenatally EE2 -exposed ovaries as compared with respective controls. Significant upregulation of the aromatase mRNA was seen in the prenatally EE2 -exposed uteri and in the EE2 -exposed ovaries. The aromatase protein was identified in all ovaries examined, and in EE2 -exposed uteri but not in controls and confirmed its localization in eutopic and ectopic glands, abnormally proliferated lesions and the lining of the cysts. Taken together, continuous EE2 exposure may cause endometriotic and precancerous lesions due to excessive estrogen synthesis in both target organs.

 

 

Hum Reprod. 2013 May;28(5):1237-46. doi: 10.1093/humrep/det044. Epub 2013 Mar 12

The prediction of pouch of Douglas obliteration using offline analysis of the transvaginal ultrasound ‘sliding sign’ technique: inter- and intra-observer reproducibility.

Reid S1Lu CCasikar IMein BMagotti RLudlow JBenzie RCondous G.

 

Abstract

STUDY QUESTION:

What is the inter-/intra-observer agreement and diagnostic accuracy among gynaecological and non-gynaecological ultrasound specialists in the prediction of pouch of Douglas (POD) obliteration (secondary to endometriosis) at offline analysis of two-dimensional videos using the dynamic real-time transvaginal ultrasound (TVS) ‘sliding sign’ technique?

SUMMARY ANSWER:

The inter-/intra-observer agreement and diagnostic accuracy for the interpretation of the TVS ‘sliding sign’ in the prediction of POD obliteration was found to be very acceptable, ranging from substantial to almost perfect agreement for the observers who specialized in gynaecological ultrasound.

WHAT IS KNOWN ALREADY:

Women with POD obliteration at laparoscopy are at an increased risk of bowel endometriosis; therefore, the pre-operative diagnosis of POD obliteration is important in the surgical planning for these women. Previous studies have used TVS to predict POD obliteration prior to laparoscopy, with a sensitivity of 72-83% and specificity of 97-100%. However, there have not been any reproducibility studies performed to validate the use of TVS in the prediction of POD obliteration pre-operatively.

STUDY DESIGN, SIZE, DURATION:

This was a reproducibility study which involved the offline viewing of pre-recorded video sets of 30 women presenting with chronic pelvic pain, in order to determine POD obliteration using the TVS ‘sliding sign’ technique. The videos were selected on real-time representative quality/quantity; they were not obtained from sequential patients. There were a total of six observers, including four gynaecological ultrasound specialists and two fetal medicine specialists. The study was conducted over a period of 1 month (March 2012-April 2012).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The four gynaecological ultrasound observers performed daily gynaecological scanning, while the other two observers were primarily fetal medicine sonologists. Each sonologist viewed the TVS ‘sliding sign’ video in two anatomical locations (retro-cervix and posterior uterine fundus), i.e. 60 videos in total. The POD was deemed not obliterated, if ‘sliding sign’ was positive in both anatomical locations (i.e. anterior rectum/rectosigmoid glided smoothly across the retro-cervix/posterior fundus, respectively). If the ‘sliding sign’ was negative (i.e. anterior rectum/rectosigmoid did not glide smoothly over retro-cervix/posterior fundal region, respectively), the POD was deemed obliterated. Diagnostic accuracy and inter-observer agreement among the six sonologists was evaluated. The same sonologist was also asked to reanalyse the same videos, albeit in a different order, at least 7 days later to assess for intra-observer agreement. A separate analysis of the inter- and intra-observer correlation was also performed to determine the agreement among the four observers who specialized in gynaecological ultrasound. Cohen’s κ coefficient <0 meant that there was poor agreement, 0.01-0.20 slight agreement, 0.21-0.40 fair agreement, 0.41-0.60 moderate agreement, 0.61-0.80 substantial agreement and 0.81-0.99 almost perfect agreement.

MAIN RESULTS AND THE ROLE OF CHANCE:

Agreement (Cohen’s κ) between all six observers for the interpretation of the ‘sliding sign’ for both sets of videos in both regions (retro-cervix and fundus) ranged from 0.354 to 0.927 (fair agreement to almost perfect agreement) compared with 0.630-0.927 (substantial agreement to almost perfect agreement) when only the gynaecological sonologists were included. The overall multiple rater agreement for the interpretation of the ‘sliding sign’ for both video sets and both regions was Fleiss’ κ 0.454 (P-value <0.01) for all six observers and 0.646 (P-value <0.01) for the four gynaecological ultrasound specialists. The multiple rater agreement for all six or all four observers was higher for the retro-cervical region versus the fundal region (Fleiss’ κ 0.542 versus 0.370 and 0.732 versus 0.560, respectively). The intra-observer agreement among the six observers for the interpretation of the ‘sliding sign’ and prediction of POD obliteration ranged from Cohen’s κ 0.60-0.95 and 0.46-1.0 (P-value <0.01), respectively. After excluding the fetal medicine specialists, the intra-observer agreement for the interpretation of the ‘sliding sign’ and the prediction of POD obliteration ranged from Cohen’s κ 0.71-0.95 and 0.67-1.0, respectively, indicating substantial to almost perfect agreement. When comparing the four gynaecological observers for the prediction of POD obliteration using the TVS ‘sliding sign’ (after excluding cases with the POD outcome classified as ‘unsure’ by the observers), the results for accuracy, sensitivity, specificity, positive and negative predictive value were 93.1-100, 92.9-100, 90.9-100, 77.8-100 and 97.7-100%, respectively.

LIMITATIONS, REASONS FOR CAUTION:

The ‘gold standard’ for the diagnosis of POD obliteration is laparoscopy; however, laparoscopic data were available only for 24 out of 30 (80%) TVS ‘sliding sign’ cases included in this study. Although this should not affect the inter- and intra-observer agreement findings, the ability to draw conclusions regarding the diagnostic accuracy of the TVS ‘sliding sign’ in the prediction of POD obliteration is somewhat limited. In addition, the diagnostic accuracy findings should be interpreted with the caveat that the cases classified as ‘unsure’ for the prediction of POD obliteration were excluded from the analysis.

WIDER IMPLICATIONS OF THE FINDINGS:

We have validated the dynamic real-time TVS ‘sliding sign’ technique for the prediction of POD obliteration, and this simple ultrasound-based test appears to have very acceptable inter-/intra-observer agreement for those who are experienced in gynaecological ultrasound. Given that women with POD obliteration at laparoscopy have an increased risk of bowel endometriosis and requirement for bowel surgery, the TVS ‘sliding sign’ test should be considered in the pre-operative imaging work-up for all women with suspected endometriosis, to allow for appropriate surgical planning. We believe the TVS ‘sliding sign’ technique may be easily learned by sonologists/sonographers who are familiar with performing gynaecological ultrasound, and that further studies are required to confirm the diagnostic accuracy of this new ultrasound technique amongst sonologists/sonographers with various levels of experience.

STUDY FUNDING/COMPETING INTEREST(S):

This study received no specific grant from any funding agency in the public, commercial or not-for-profit sectors and the authors declare no competing interests.

 

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