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Pag. 11

Hum Reprod Update.2012 May-Jun;18(3):248-59. Epub 2012 Feb 26.

Principles of phenomics in endometriosis.

Viganò P, Somigliana E, Panina P, Rabellotti E, Vercellini P, Candiani M.


Obstetrics and Gynecology Unit, San Raffaele Scientific Institute, Milano, Italy.



Endometriosis has been associated with specific morphometric characteristics and pigmentary traits. The purpose of this study was to systematically review prior publications dealing with this aspect in order to revisit phenotypic information in the context of phenomics principles.


Comprehensive searches of Pubmed, Medline and Embase were conducted to identify studies, published from 1990 to 2011 in the English language literature, on the relationship between endometriosis and morphometric characteristics/pigmentary traits.


We identified 11 studies on the association between endometriosis and body mass index (BMI) in the adult population and 5 studies on the same association during early life. While a modest inverse correlation was found between endometriosis and adult BMI, a stronger association was consistently demonstrated between endometriosis and early life body size, even after adjusting for confounding factors such as age, birthweight, age at menarche, parity and oral contraceptive use. Four papers have been published on the association between endometriosis and cutaneous naevi and five on the association between the disease and specific pigmentary traits. A skin phenotype characterized by the presence of naevi and freckles and by a high sensitivity to sun exposure is represented more frequently in women with endometriosis.


Endometriosis appears to be associated with some phenotypic variations likely attributable to the strong effect of the environment on the expression and function of genes influencing the traits. Novel clues on endometriosis pathogenesis may derive from the analysis of the phenotypic traits associated with the disease.

Indian Heart J.2012 May-Jun;64(3):305-8.

Uterine artery embolisation.

Bhardwaj R.


Professor, Department of Cardiology, Indira Gandhi Medical College, Shimla – 171001.



Fibroids are commonest benign tumour of the uterus. It presents with bleeding per vagina in most of the cases. Surgical treatment consists of myomectomy or hysterectomy with or without salpingo oophrectomy, with its inherent morbidity, prolonged hospital stay and psychosocial problems. Surgery is not the best option especially in unmarried and nullipara.


Thirty-five patients were subjected to uterine artery embolisation (UAE). Mean age was 35.51 ± 7.36 years. Two patients were suffering from advanced carcinoma of cervix, 32 had fibroid of uterus, one had endometriosis. Three patients were unmarried, three did not have any issue, three had associated haemodynamically significant cardiac disorders, one had polycystic renal disease, and one had hypernephroma. Four patients had multiple fibroids. The UAE was done through contralateral femoral artery puncture, bilaterally, with the help of Judkin’s right coronary catheter. Ultrasound was repeated after 3 months.


The UAE was successful in all patients. Mean procedural time was 75 minutes. Hospital stay was 1 day only. Bleeding stopped in all 35 patients. One patient had recurrence of bleeding after 2 months and underwent surgery. Fibroids disappeared in eight patients, decreased in size by > 75% in 11 patients, and by 50-75% in six patients. Five patients did not report back with ultrasound. Two patients had normal delivery after UAE.


Uterine artery embolisation is effective therapy to stop uterine bleeding. It is effective in controlling the symptoms in uterine fibroids and also decreases the size of fibroids. Hospital stay is only 1 day.

Int J Colorectal Dis.2012 May;27(5):681-2. Epub 2011 Jun 23.

Endometrioid adenocarcinoma arising from colonic endometriosis in a Lynch syndrome patient.

Chen PC, Chao SC, Hsu KF, Lee CT, Lee JC.

Int J Gynecol Cancer.2012 May;22(4):539-45.

Transmembrane estrogen receptor GPR30 is more frequently expressed in malignant than benign ovarian endometriotic cysts and correlates with MMP-9 expression.

Long L, Cao Y, Tang LD.


Department of Obstetrics and Gynecology, First Affiliated Hospital, Chongqing Medical University, Chongqing, China.



Molecular studies supporting the idea of malignant transformation of endometriosis are sparse and not well substantiated. The aims of this study were to detect expression levels of the novel estrogen-responsive receptor G protein-coupled estrogen receptor 1 GPER, also termed GPR30, and to determine its correlation with matrix metalloproteinase-9 (MMP-9) in benign and malignant ovarian endometriotic cysts and to explore the significance of GPR30.


Immunohistochemical staining with the streptavidin-peroxidase method was conducted to determine the expression of GPR30 and MMP-9 in 24 cases of endometriosis-associated ovarian carcinoma (EAOC) and 32 specimens of ovarian endometriosis without malignant transformation. Reverse transcriptase polymerase chain reaction was performed to determine messenger RNA expression of GPR30 and MMP-9 in benign and malignant ovarian endometriotic cysts. We also investigated their associations with known clinic pathological parameters and the interrelationship between the expressions of the 2 proteins.


The positive staining ratio of GPR30 was 95.8% (23/24) in EAOC cases, and the HScore was 268; whereas the positive ratio was 25% (8/32) in benign endometriotic cysts, and the Hscore was 95. Matrix metalloproteinase-9 was expressed in all 24 EAOC cases and 87.5% (28/32) of the benign samples, and the Hscores were 280 and 260, respectively (P > 0.05). The receptor GPR30 was significantly higher in EAOCs than in benign endometriotic cysts (P < 0.05). The expression of GPR30 messenger RNA was also significantly higher in malignant ovarian endometriotic cysts than in the benign group. The receptor GPR30 was positively related to tumor size, tumor stage, and lymph node metastasis. A positive relationship between GPR30 and MMP-9 was found (P = 0.002).


The results suggest that the abnormal expression of GPR30 may be involved in malignant transformation, invasion, and metastasis of EAOCs. Testing of GPR30 expression levels may present both diagnostic and therapeutic options for the treatment of ovarian malignancies.

Int J Gynecol Cancer.2012 May;22(4):531-8.

Different levels of sialyl-Tn antigen expressed on MUC16 in patients with endometriosis and ovarian cancer.

Akita K, Yoshida S, Ikehara Y, Shirakawa S, Toda M, Inoue M, Kitawaki J, Nakanishi H, Narimatsu H, Nakada H.


Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto, Japan.



Although CA125 antigen is a useful marker for ovarian cancer, its expression is also elevated in endometriosis. The purpose of this study was to develop an assay method for evaluating differentially glycosylated MUC16 (CA125 core protein) in patients with endometriosis and ovarian cancer.


We prepared MUC16-enriched fractions from peritoneal fluid of patients with endometriosis and conditioned medium of ovarian carcinoma-3 cells by gel filtration, and evaluated the expression of sialyl-Le, Tn, and sialyl-Tn antigens by dot blot analysis. A sandwich enzyme-linked immunosorbent assay was developed to measure the level of sialyl-Tn antigen expressed on MUC16 (sTn/MUC16). The level of sTn/MUC16 was compared between patients with endometriosis (n = 21) and ovarian cancer (n = 36) and in ovarian cancers with different clinical diagnostic criteria. Furthermore, distribution of MUC16 and sialyl-Tn antigen in ovarian cancer tissues was observed immunohistochemically.


Sialyl-Tn antigen was markedly detectable in the MUC16-enriched fractions from conditioned medium of ovarian carcinoma-3 cells but negligible in those from the peritoneal fluid of the patients with endometriosis. The level of sTn/MUC16 determined by a sandwich enzyme-linked immunosorbent assay was significantly higher in the patients with ovarian cancer than that in the patients with endometriosis (P < 0.001). An elevated level of sTn/MUC16 was detected in 44% of the patients with ovarian cancer but not all the patients with endometriosis. This level increased more prominently in the patients with ovarian cancer than that of MUC16 as both the clinical stage and cytological grade advanced. An elevated level of sTn/MUC16 was frequently found in the patients with serous and endometrioid carcinomas. Consistent with this, sialyl-Tn antigen was colocalized with MUC16 in serous and endometrioid ovarian cancer tissues.


Estimation of the sTn/MUC16 level may be useful for discriminating endometriosis from ovarian cancer and for evaluating the clinical stage, cytological grade, and histological type of ovarian cancer.

Int J Gynecol Pathol.2012 May;31(3):254-63.

Aberrant expression of the mammalian target of rapamycin, hypoxia-inducible factor-1α, and glucose transporter 1 in the development of ovarian clear-cell adenocarcinoma.

Kato M, Yamamoto S, Takano M, Matsubara O, Furuya K.


Departments of Obstetrics and Gynecology, National Defense Medical College, Tokorozawa, Saitama, Japan.


Ovarian clear-cell adenocarcinoma (CCA) is known to be a type of cancer in humans with a high frequency of expression of the mammalian target of rapamycin (mTOR), hypoxia-inducible factor-1 (HIF-1), and glucose transporter 1 (Glut1). In this study, we aimed to determine how these alterations contribute to tumor development of CCAs. Immunohistochemical expressions of phosphorylated-mTOR (p-mTOR), HIF-1α, and Glut1 were analyzed in 36 CCAs and 60 coexistent putative precursor lesions: 19 nonatypical and 16 atypical endometriotic lesions, and 11 benign and 14 borderline clear-cell adenofibroma (CCAF) components. Twenty-one cases with solitary endometriosis were also examined. The frequencies of immunopositivity for p-mTOR (in cytoplasm or nucleus), HIF-1α (in nucleus), and Glut1 increased in accordance with higher cytological atypia in the putative precursors: 58%, 5%, and 16% in the nonatypical endometriosis; 63%, 37%, and 50% in the atypical endometriosis; 77%, 95%, and 95% in the endometriosis-associated CCAs; 27%, 0%, and 0% in the benign-CCAF components; 64%, 79%, and 43% in the borderline CCAF components; and 71%, 100%, and 93% in the CCAF-associated CCAs, respectively. p-mTOR, HIF-1α (in the nucleus), and Glut1 were positive in 10%, 5%, and 19% of the solitary endometriosis, respectively. In the putative precursor lesions coexisting with CCA, a strong correlation in the expression between p-mTOR and HIF-1α and between HIF-1α and Glut1 was identified. Expressions of p-mTOR, HIF-1α, and Glut1 have already been evident in the putative precursor lesions of CCA, and these alterations cumulatively occur in the development of ovarian CCA.

Int J Urol.2012 May;19(5):429-36. doi: 10.1111/j.1442-2042.2012.02966.x. Epub 2012 Feb 21.

Transient receptor potential A1 receptor-mediated neural cross-talk and afferent sensitization induced by oxidative stress: implication for the pathogenesis of interstitial cystitis/bladder pain syndrome.

Furuta A, Suzuki Y, Hayashi N, Egawa S, Yoshimura N.


Department of Urology, Jikei University School of Medicine, Tokyo, Japan. a-furuta@rf7.so-net.ne.jp


Although the pathogenesis of interstitial cystitis/bladder pain syndrome remains unknown, there is a significant correlation of interstitial cystitis/bladder pain syndrome with other chronic pain disorders, such as irritable bowel syndrome, endometriosis and fibromyalgia syndrome. In this review, we highlight evidence supporting neural cross-talk in the dorsal root ganglia, spinal cord and brain levels, which might play a role in the development of chronic pain disorders through central sensitization. In addition, we focus on transient receptor potential V1 and transient receptor potential A1 as the receptor targets for chronic pain conditions, because transient receptor potential V1 and transient receptor potential A1 act as a nocisensor to mediate not only an afferent signal to the dorsal horn of the spinal cord, but also an efferent signal in the periphery through secretion of inflammatory agents, such as substance P and calcitonin gene-related peptide in nociceptive sensory neurons. Furthermore, peripheral inflammation produces multiple inflammatory mediators that act on their cognate receptors to activate intracellular signal transduction pathways and thereby modify the expression and function of transient receptor potential V1 and transient receptor potential A1 (peripheral sensitization). During tissue damage and inflammation, oxidative stress, such as reactive oxygen species or reactive carbonyl species is also generated endogenously. The highly diffusible nature might account for the actions of free radical formation far from the site of injury, thereby producing systemic pain conditions without central sensitization through neural cross-talk. Because oxidative stress is considered to induce activation of transient receptor potential A1, we also discuss exogenous and endogenous oxidative stress to elucidate its role in the pathogenesis of interstitial cystitis/bladder pain syndrome and other chronic pain conditions.

J Appl Toxicol.2012 May;32(5):318-32. doi: 10.1002/jat.1771. Epub 2011 Dec 12.

Cadmium a metalloestrogen: are we convinced?

Silva N, Peiris-John R, Wickremasinghe R, Senanayake H, Sathiakumar N.


Faculty of Medical Sciences, University of Sri Jayewardenepura, Sri Lanka. yasanga78@yahoo.com


Metalloestrogens are inorganic metal ions that bind to and activate oestrogen receptors. They are implicated in the aetiology of oestrogen-dependent diseases such as cancers of the breast and endometrium as well as endometriosis. Cadmium is one of the most studied metalloestrogens. In this review, scientific evidence for the oestrogenic effects of cadmium is critically evaluated to determine if there is sufficient evidence to support cadmium as an aetiological factor of oestrogen-dependent disease in humans. Results of the review indicated that, although the in vitro and in vivo evidence of the oestrogenic properties of cadmium was persuasive, evidence from population-based human studies remains conflicting. Considerable knowledge gaps exist on the potential oestrogenic effect of cadmium in humans. Research that focuses on bridging these knowledge gaps would be useful in preventing and managing oestrogen-dependent disease in humans.

J Gen Intern Med.2012 May;27(5):603-7. Epub 2012 Jan 11.

Thoracic endometriosis unmasked by ovarian hyperstimulation for in vitro fertilization.

Halvorson SA, Ricker MA, Barker AF, Patton PE, Harrison RA, Hunter AJ.


OHSU Division of Hospital Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd BTE-119, Portland, Oregon 97239, USA. halvorss@ohsu.edu


Thoracic endometriosis syndrome is a well-described, rare manifestation of endometriosis. We present a case of a 35-year old woman undergoing controlled ovarian stimulation prior to in vitro fertilization (IVF) who developed bilateral hemorrhagic pleural effusions. She was initially diagnosed with ovarian hyperstimulation syndrome, a complication of infertility therapy; however, she was later found to have occult thoracic endometriosis. We describe ovarian hyperstimulation syndrome and review the manifestations of thoracic endometriosis syndrome. Although endometriosis is a hormone-dependent disease, the rate of IVF complications related to endometriosis is low.

J Minim Invasive Gynecol.2012 May-Jun;19(3):396-400.

Sacral nerve infiltrative endometriosis presenting as perimenstrual right-sided sciatica and bladder atonia: case report and description of surgical technique.

Lemos N, Kamergorodsky G, Ploger C, Castro R, Schor E, Girão M.


Department of Gynecology, Pelvic Neurodysfunction Clinic, Federal University of São Paulo, São Paulo, Brazil. nucelio@gmail.com


Endometriosis infiltrating the sacral nerve roots is a rarely reported manifestation of the disease. The objectives of this article are to report such a case and to describe the surgical technique for laparoscopic decompression of sacral nerve roots and treatment of endometriosis at this site. The patient as a 38-year-old woman who had undergone 2 previous laparoscopic procedures for electrocoagulation of peritoneal endometriosis and self-reported perimenstrual right-sided sciatica and urinary retention. Clinical examination revealed allodynia (pain from a stimulus that does not normally cause pain) on the S2 to S4 dermatomes and hypoesthesia on part of the S3 dermatome. Magnetic resonance imaging showed an endometriotic nodule infiltrating the anterior rectal wall. Laparoscopic exploration of the sacral nerve roots demonstrated vascular compression of the lumbosacral trunk and endometriosis entrapping the S2 to S4 sacral nerve roots, with an endometrioma inside S3. The endometriosis was removed from the sacral nerve roots and detached from the sacral bone, and a nodulectomy of the anterior rectal wall was performed. Normal urinary function was restored on postoperative day 2, and pain resolved after a period of post-decompression. Intrapelvic causes of entrapment of sacral nerve roots are rarely described in the current literature, either because of misdiagnosis or actual rareness of the condition. Recognition of the clinical markers for these lesions may lead to an increase in diagnosis and specific treatment.

J Minim Invasive Gynecol.2012 May-Jun;19(3):380-2.

Disseminated peritoneal leiomyomatosis with endometriosis.

Mueller F, Kuehn K, Neudeck H, Siedentopf N, Ulrich U.


Department of Obstetrics and Gynecology, Martin Luther Hospital, Berlin, Germany. f.mueller@mlk-berlin.de


Herein is described the case of a 41-year-old woman with disseminated peritoneal leiomyomatosis with distinct endometriosis. The pathogenesis of both conditions is as yet unclear; however, the 2 main hypotheses are discussed. Metaplastic origin from the secondary müllerian system has been suggested, as well as metastatic development. Inasmuch as spontaneous regression is likely, and the course of the disease can be influenced by hormonal withdrawal, operative measures could be refined to ensure the correct diagnosis and benignity.

J Minim Invasive Gynecol.2012 May-Jun;19(3):317-24. Epub 2012 Feb 18.

Patients with endometriosis of the rectosigmoid have a higher percentage of natural killer cells in peripheral blood.

Dias JA Jr, Podgaec S, de Oliveira RM, Carnevale Marin ML, Baracat EC, Abrão MS.


Department of Obstetrics and Gynecology, São Paulo University, São Paulo, Brazil. jadiasjr@me.com



To estimate the concentration of natural killer (NK) cells in the peripheral blood in patients with and without endometriosis.


Case-control study (Canadian Task Force classification II-2).


Tertiary referral hospital.


One hundred fifty-five patients who had undergone videolaparoscopy were divided into 2 groups: those with endometriosis (n = 100) and those without endometriosis (n = 55).


The percentage of NK cells relative to peripheral lymphocytes was quantified at flow cytometry in 155 patients who had undergone laparoscopy. In addition to verifying the presence of endometriosis, stage of disease and the sites affected were also evaluated.


The mean (SD) percentage of NK cells was higher (15.3% [9.8%]) in patients with endometriosis than in the group without the disease (10.6% [5.8%]) (p < .001). The percentage of NK cells was highest (19.8 [10.3%]) in patients with advanced stages of endometriosis and in those in whom the rectosigmoid colon was affected. In a statistical model of probability, the association of this marker (NK cells ≥11%) with the presence of symptoms such as pain and intestinal bleeding during menstruation and the absence of previous pregnancy yielded a 78% likelihood of the rectosigmoid colon being affected.


Compared with patients without endometriosis, those with endometriosis demonstrate a higher concentration of peripheral NK cells. The percentage of NK cells is greater, primarily in patients with advanced stages of endometriosis involving the rectosigmoid colon. Therefore, it may serve as a diagnostic marker for this type of severe endometriosis, in particular if considered in conjunction with the symptoms.

J Obstet Gynaecol Res.2012 May;38(5):810-6. doi: 10.1111/j.1447-0756.2011.01805.x. Epub 2012 Mar 22.

Evaluation of N-acetilglucosaminidase and myeloperoxidase activity in patients with endometriosis-related infertility undergoing intracytoplasmic sperm injection.

Lamaita RM, Pontes A, Belo AV, Caetano JP, Andrade SP, Cândido EB, Carneiro MM, Silva-Filho AL.


Department of Obstetrics and Gynecology, Paulista State University, Botucatu, Brazil.



Inflammation is as an important factor in ovulation with the active participation of leucocytes and their inflammatory mediators. The present study was performed to compare the activity of the inflammatory enzymes myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) in patients with endometriosis-related infertility and in normally ovulating women undergoing intracytoplasmic sperm injection (ICSI).


This prospective study included infertile women undergoing ICSI treatment. These women were divided into two groups: endometriosis anovulation (n = 18) and normally ovulating (n = 20). NAG and MPO activity was evaluated colorimetrically in serum and in follicular fluids obtained at the time of oocyte retrieval.


There was a significant correlation between the serum and follicular fluid activities of NAG and MPO (τ = 0.256, P = 0.025; and τ = -0.234, P = 0.041; respectively). Both serum and follicular fluid NAG activities were higher in patients with endometriosis compared to the control group (P < 0.001). MPO follicular fluid activity was lower in patients with endometriosis compared to normally ovulating women (P = 0.016).


Infertile patients with endometriosis show a distinct pattern of serum and follicular fluid macrophage/neutrophil activation compared to normally ovulating women undergoing ICSI, which may reflect the role of immune and inflammatory alterations in endometriosis-related infertility.

© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

J Obstet Gynaecol Res.2012 May;38(5):899-902. doi: 10.1111/j.1447-0756.2011.01783.x. Epub 2012 Mar 13.

Endometrial stromal sarcoma arising from endometriosis of the terminal ileum: the role of immunohistochemistry in the differential diagnosis.

Biliatis I, Akrivos N, Sotiropoulou M, Rodolakis A, Simou M, Antsaklis A.


First Department of Obstetrics and Gynecology, Alexandra Hospital, Athens, Greece. giannisbil@hotmail.com


Low-grade endometrial stromal sarcoma (LESS) is an uncommon uterine malignancy. Occasionally, it may develop in extrauterine endometriotic lesions and present morphological characteristics mimicking various neoplasms, making its diagnosis very challenging. We report a rare case of a 56-year-old woman presenting with a pelvic mass, initially presumed to be of ovarian origin. After surgical excision the diagnosis of a LESS arising from foci of endometriosis of the terminal ileum was established. Pelvic lymph nodes and omentum were also infiltrated. The patient received adjuvant chemotherapy and medroxyprogesterone; she is alive with no evidence of disease after a follow-up of 38 months. Immunohistochemical characteristics of the tumor are very important for the differential diagnosis of this rare neoplasm and include diffuse strong positivity for CD 10, estrogen receptor expression and CD 34 negativity.

J Steroid Biochem Mol Biol.2012 May;130(1-2):16-25. Epub 2012 Jan 8.

Expression of human aldo-keto reductase 1C2 in cell lines of peritoneal endometriosis: potential implications in metabolism of progesterone and dydrogesterone and inhibition by progestins.

Beranič N, Brožič P, Brus B, Sosič I, Gobec S, Lanišnik Rižner T.


Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.


The human aldo-keto reductase AKR1C2 converts 5α-dihydrotestosterone to the less active 3α-androstanediol and has a minor 20-ketosteroid reductase activity that metabolises progesterone to 20α-hydroxyprogesterone. AKR1C2 is expressed in different peripheral tissues, but its role in uterine diseases like endometriosis has not been studied in detail. Some progestins used for treatment of endometriosis inhibit AKR1C1 and AKR1C3, with unknown effects on AKR1C2. In this study we investigated expression of AKR1C2 in the model cell lines of peritoneal endometriosis, and examined the ability of recombinant AKR1C2 to metabolise progesterone and progestin dydrogesterone, as well as its potential inhibition by progestins. AKR1C2 is expressed in epithelial and stromal endometriotic cell lines at the mRNA level. The recombinant enzyme catalyses reduction of progesterone to 20α-hydroxyprogesterone with a 10-fold lower catalytic efficiency than the major 20-ketosteroid reductase, AKR1C1. AKR1C2 also metabolises progestin dydrogesterone to its 20α-dihydrodydrogesterone, with 8.6-fold higher catalytic efficiency than 5α-dihydrotestosterone. Among the progestins that are currently used for treatment of endometriosis, dydrogesterone, medroxyprogesterone acetate and 20α-dihydrodydrogesterone act as AKR1C2 inhibitors with low μM K(i) values in vitro. Their potential in vivo effects should be further studied.

J Ultrasound Med.2012 May;31(5):809-11.

Incidental finding of decidualized vesical endometriosis in an asymptomatic obstetrical patient.

Faske EJ, Mack LM, Ozcan T.

Kyobu Geka.2012 May;65(5):374-9.

Evaluation for medical management on catamenial pneumothorax

[Article in Japanese]

Hasumi T, Hoshi F, Saito Y, Tanaka R, Ishiki Y.


Department of Thoracic Surgery, Sendai Medical Center, Sendai, Japan.


Catamenial pneumothorax (CP) is one of the clinical manifestations of endometriosis, therefore the systemic hormonal therapy is indispensable and should be the 1st choice for CP treatment. However, it is refractory and repeats a recurrence, so that a combined or sequential adjuvant treatment becomes necessary. From 2003 to 2009, 5 patients with CP were treated at our institution. All patients had right-sided pneumothorax and the history of pelvic endometriosis. By thoracoscopic examination, diaphragmatic abnormalities, such as defect, pinhole, or brown spot, were identified in all patients. We performed hormonal therapy combined with chemical pleurodesis using OK-432, as an initial treatment. Two patients have been free of recurrence for 24 and 53 months, respectively. Three patients who refused or interrupted hormonal therapy caused a recurrence, but were successfully managed with the addition of pleurodesis and continuing hormonal therapy. At present, all patients are asymptomatic with 13 to 92 months recurrence-free period. From the long-term results, our therapeutic strategy consisted of hormonal therapy and chemical pleurodesis is considered appropriate.

Lancet Oncol.2012 May;13(5):e189-90; author reply e190.

Endometriosis and ovarian cancer.

Guo SW, Zilberberg MD, Hummelshoj L.

Comment on

Lancet Oncol.2012 May;13(5):e188-9.

Endometriosis and ovarian cancer.

Vercellini P, Somigliana E, Buggio L, Bolis G, Fedele L.

Comment on

Mol Hum Reprod.2012 May;18(5):280-7. Epub 2011 Dec 19.

Association of E-cadherin single nucleotide polymorphisms with the increased risk of endometriosis in Indian women.

Govatati S, Tangudu NK, Deenadayal M, Chakravarty B, Shivaji S, Bhanoori M.


Department of Biochemistry, Osmania University, Hyderabad 500 007, India.


The objective of the present study was to investigate the association between gene E-cadherin single nucleotide polymorphisms (SNPs) and risk of developing endometriosis in Indian women and to evaluate the role of E-cadherin expression in the pathophysiology of endometriosis. A genetic association study was conducted in 715 endometriosis cases and 500 controls of Indian origin. We genotyped -160 C/A, +54 C/T and -347 G/GA SNPs of gene E-cadherin by PCR-sequencing and PCR-restriction fragment length polymorphism techniques. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D’) for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand genetic contributions to the pathophysiology of endometriosis, the expression pattern of E-cadherin in the endometrium of women with and without endometriosis was analyzed by western blot and immunohistochemical analysis. The frequencies of -347GA/GA (P = 0.026) and -160A/A (P = 0.0019) genotypes and -347G/-160A/+54C (P = 0.007) and -347GA/-160A/+54C (P < 0.0001) haplotypes were significantly different between patients and controls. Strong LD was observed between -347G/GA and -160C/A loci (D’ = 0.64) when compared with -347G/GA and +54C/T (D’ = 0.585) or -160C/A and +54C/T (D’ = 0.05) loci in cases. Furthermore, increased membranous E-cadherin expression was observed in cases than in controls. The expression seems to be genotype dependent. In conclusion, the E-cadherin -347GA/GA and -160A/A genotypes and -347GA/-160A/+54C and -347G/-160A/+54C haplotypes may jointly modify the risk of endometriosis in Indian women. In addition, the differential expression of E-cadherin may play an important role in pathogenesis of endometriosis.

Pain.2012 May;153(5):1006-14. Epub 2012 Mar 2.

Changes in regional gray matter volume in women with chronic pelvic pain: a voxel-based morphometry study.

As-Sanie S, Harris RE, Napadow V, Kim J, Neshewat G, Kairys A, Williams D, Clauw DJ, Schmidt-Wilcke T.


Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA.


Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15%-20% of women in the United States. Endometriosis is often associated with CPP, however, other factors, such as preexisting or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing. Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, and 23 healthy controls. All patients with endometriosis and/or CPP were surgically confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception, including the left thalamus, left cingulate gyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis who had no CPP. We conclude that CPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis.

Pediatr Radiol.2012 May;42(5):636-40. Epub 2011 Sep 13.

Radiologic findings of pelvic venous congestion in an adolescent girl with angiographic confirmation and interventional treatment.

Wassong C, Shah B, Kanayama M, Bjarnason H, Milla SS.


Department of Radiology, New York University Langone Medical Center, New York, NY 10016, USA. carolyn.wassong@gmail.com


We present a case of pelvic venous congestion in a 13-year-old girl who complained of pelvic pain for 9 months. The diagnosis of pelvic congestion syndrome was suggested by imaging modalities, including sonography, CT and MRI, with classically described imaging findings. The girl underwent diagnostic laparoscopy, where visual inspection demonstrated congested pelvic veins and endometriosis. After removal of endometrial implants, the child’s pain persisted and she subsequently underwent venography and embolization of the ovarian veins. We found no literature describing pelvic venous congestion (PVC) in children. Knowledge that PVC exists in children is important, particularly for pediatric radiologists who are imaging patients with complaints of pelvic pain.

Radiographics.2012 May-Jun;32(3):845-63.

MR imaging of malignancies arising in endometriomas and extraovarian endometriosis.

McDermott S, Oei TN, Iyer VR, Lee SI.


Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, White 270, Boston, MA 02114, USA. mcdermottshaunagh@gmail.com


Cancers that arise in ovarian or extraovarian endometriosis are a distinct disease category with a histologic profile different from that of the more common epithelial ovarian cancers and with a better prognosis. Because the malignant transformation of endometriomas is rarely associated with lymphadenopathy or peritoneal carcinomatosis, a high index of suspicion on the part of the radiologist is necessary to establish a timely diagnosis of endometriosis-related ovarian cancers and allow appropriate oncologic management. Although imaging is not currently performed for surveillance of endometriosis, magnetic resonance (MR) imaging is often performed when surgical treatment is under consideration. An optimal MR imaging protocol for the detection of cancer arising in an endometrioma includes a review of subtraction images derived from unenhanced and contrast material-enhanced T1-weighted datasets. Subtraction images provide improved conspicuity of enhancing mural nodules–which are the most sensitive MR imaging sign of malignancy in ovarian endometriosis–against the background of the high-signal-intensity endometriotic cyst. Cancers arising in extraovarian endometriosis typically manifest as solid lesions with intermediate signal intensity on T1- and T2-weighted images, enhancement after the intravenous administration of a gadolinium-based contrast material, and restricted diffusion on diffusion-weighted images and apparent diffusion coefficient (ADC) maps. The signal intensity of myometrium, or, if the uterus is absent, that of the small bowel wall, is used as an internal reference standard for lesion signal intensity. Lesions are considered to have restricted diffusion if they show signal hyperintensity relative to the reference structure on diffusion-weighted images and hypointensity or isointensity relative to that structure on ADC maps. For definitive diagnosis, histopathologic analysis is required.

Reprod Biomed Online.2012 May;24(5):496-502. Epub 2012 Jan 31.

The eutopic endometrium in endometriosis: are the changes of clinical significance?

Brosens I, Brosens JJ, Benagiano G.


Leuven Institute for Fertility and Embryology, Leuven, Belgium. ivo.brosens@med.kuleuven.be


The eutopic endometrium in women suffering from endometriosis is different in many ways from that of healthy controls. Both proliferative and secretory eutopic endometria exhibit changes in endometriosis with heterogeneous responses. In addition, nerve fibres appear in the endometrium and myometrium of these women. The endometrium is a rich source of pro-angiogenic factors and vascular events are often disrupted in endometriosis with an overall increase in angiogenesis. A number of investigations have shown that endometriosis is likely the most common cause of endometrial receptivity defects. Endometriosis is also associated with relative 17β-hydroxysteroid dehydrogenase type II deficiency and these molecular aberrations indicate that local oestrogen production sustains ectopic implants. Recently it has been shown that endometriosis, as a chronic inflammatory disorder, disrupts co-ordinated progesterone response throughout the reproductive tract, including the endometrium, leading to a condition of ‘progesterone resistance’. Investigators have searched for biomarkers of endometriosis, but these investigations are fraught with methodological difficulties. In conclusion, molecular phenotyping of the endometrium is changing the disease paradigm, from being foremost an oestrogen-dependent disease to a disorder characterized primarily by progesterone resistance. In recent years, research on the pathogenesis of endometriosis has been focused on alterations in the uterus and particularly the eutopic endometrium. The eutopic endometrium in women suffering from endometriosis is different in many ways from that of healthy controls. Both proliferative and secretory eutopic endometria exhibit changes in endometriosis with heterogeneous responses. The endometrium is a rich source of pro-angiogenic factors and vascular events are often disrupted in endometriosis with an overall increase in angiogenesis. A number of investigations have shown that endometriosis is likely the most common cause of endometrial receptivity defects. Recently, it has been shown that endometriosis, as a chronic inflammatory disorder, disrupts co-ordinated progesterone response throughout the reproductive tract, including the endometrium, leading to a condition of ‘progesterone resistance’. Investigators have searched for biomarkers of endometriosis, but these investigations are fraught with methodological difficulties. In conclusion, molecular phenotyping of the endometrium is changing the disease paradigm; from being foremost an oestrogen-dependent disease to a disorder characterized primarily by progesterone resistance.

Reprod Biomed Online.2012 May;24(5):547-9. Epub 2012 Jan 31.

Successful pregnancy outcome following gamete intra-Fallopian transfer in a patient with Müllerian dysgenesis.

Lee CS, Lie AT.


Alpha International Fertility Centre, 31, Level 2, Jalan PJU 5/6, Dataran Sunway, Kota Damansara 47810, Petaling Jaya, Selangor, Malaysia. colinleess@yahoo.com


A 29-year-old lady with Müllerian dysgenesis was keen to have a baby. Clinically, she was medium built with well-developed secondary female sexual characteristics. There was a short and blind vagina. She had undergone surgery for an imperforated hymen. Her FSH and LH concentrations were normal. Laparoscopy revealed a patent right Fallopian tube, a rudimentary right uterus and extensive pelvic endometriosis. She subsequently underwent gamete intra-Fallopian transfer (GIFT). Oocyte retrieval was carried out laparoscopically and a total of nine oocytes were retrieved. Four of the oocytes were transferred together with motile spermatozoa into the right Fallopian tube and the remaining five oocytes were inseminated with spermatozoa for IVF. Three embryos resulted and were frozen. She subsequently developed moderate ovarian hyperstimulation syndrome. Serum β-human chorionic gonadotrophin concentration 14 days after GIFT was 1612 IU/l. Her antenatal care was relatively uneventful until 31 weeks of gestation when she was diagnosed to have intrauterine growth retardation and oligohydramnios. She then underwent an emergency Caesarean section at 32 weeks of pregnancy delivering a normal baby. This case study describes a successful pregnancy outcome following gamete intra-Fallopian transfer (GIFT) in a woman with malformation of the vagina (Müllerian dysgenesis). A 29-year-old lady with Müllerian dysgenesis diagnosed at 16 years of age was keen to become pregnant. Upon examination, a decision was made for a William’s vulvovaginoplasty but as the patient was indecisive the surgery was deferred. Clinically, she is a medium-built lady with well-developed secondary female sexual characteristics. There was a short and blind vagina. Her serum FSH and LH concentrations were normal. Laparoscopy revealed a patent right Fallopian tube, a rudimentary right uterus and extensive pelvic endometriosis. She subsequently underwent GIFT. Nine oocytes were retrieved through laparoscopy. Four of the oocytes were transferred together with motile sperm into the right Fallopian tube and the remaining five oocytes were inseminated with sperm for IVF. Three embryos resulted and were frozen. Serum β human chorionic gonadotrophin concentration measured 14 days after GIFT was 1612 IU/l. An abdominal ultrasonography performed at 5 weeks showed one intrauterine gestational sac. Her antenatal care was uneventful until 31 weeks of gestation when she developed a deficiency of amniotic fluid in the amniotic sac. She then underwent an emergency Caesarean section at 32 weeks of pregnancy. She delivered a healthy, normal 1.24 kg baby boy. Her post-natal care was uneventful.

Reprod Sci.2012 May;19(5):483-92. Epub 2012 Feb 16.

HDAC1 and HDAC2 are differentially expressed in endometriosis.

Colón-Díaz M, Báez-Vega P, García M, Ruiz A, Monteiro JB, Fourquet J, Bayona M, Alvarez-Garriga C, Achille A, Seto E, Flores I.


Department of Microbiology, Ponce School of Medicine and Health Sciences, Ponce, PR 00731, USA.


Epigenetic mechanisms have been ascribed important roles in endometriosis. Covalent histone modifications at lysine residues have been shown to regulate gene expression and thus contribute to pathological states in many diseases. In endometriosis, histone deacetylase inhibition (HDACi) resulted in reactivation of E-cadherin, attenuation of invasion, decreased proliferation of endometriotic cells, and caused lesion regression in an animal model. This study was conducted to assess basal and hormone-regulated gene expression levels of HDAC1 and HDAC2 (HDAC1/2) in cell lines and protein expression levels in tissues. Basal and steroid hormone-regulated HDAC1/2 gene expression levels were determined by quantitative polymerase chain reaction in cell lines and tissues. Protein levels were measured by immunohistochemistry (IHC) in tissues on an endometriosis tissue microarray (TMA). Basal HDAC1/2 gene expression levels were significantly higher in endometriotic versus endometrial stromal cells, which was confirmed by Western blot analysis. Estradiol (E2) and progesterone (P4) significantly downregulated HDAC1 expression in endometrial epithelial cells. Levels of HDAC2 were upregulated by E2 and downregulated by E2 + P4 in endometrial stromal cells. Hormone modulation of HDAC1/2 gene expression was lost in the endometriotic cell line. Immunohistochemistry showed that HDAC1/2 proteins were expressed in a substantial proportion of lesions and endometrium from patients, and their expression levels varied according to lesion localization. The highest proportion of strong HDAC1 immunostaining was seen in ovarian, skin, and gastrointestinal lesions, and of HDAC2 in skin lesions and endometrium from patients with endometriosis. These studies suggest that endometriosis etiology may be partially explained by epigenetic regulation of gene expression due to dysregulations in the expression of HDACs.

Transplant Proc.2012 May;44(4):1067-9.

Induction of regulatory CD4 cells and prolongation of survival of fully allogeneic murine cardiac grafts by danazol.

Uchiyama M, Jin X, Zhang Q, Amano A, Watanabe T, Niimi M.


Department of Cardiovascular Surgery, Juntendo University Hospital, Tokyo, Japan.


Danazol, a modified testosterone, has been used to treat endometriosis and pretreatment before in vitro fertilization and embryo transfer, although its reproductive mechanisms remain unclear. We investigated the effect of danazol on alloimmune responses in murine heart transplantation. CBA male mice (H2(k)) that underwent transplantation of C57BL/6 (B6, H2(b)) hearts received danazol (0.4 and 4 mg/kg/d) by intraperitoneal injection from the day of transplantation to days 6. We performed an adoptive transfer study to determine regulatory cells as well as cell proliferation, cytokine, and flow cytometry assessments. Danazol-treated (4 mg/kg/d) CBA mice showed prolonged allograft survival (median survival time [MST], 63 days). Moreover, secondary CBA recipients of whole splenocytes and CD4(+) cells from primary danazol-treated (4 mg/kg/d) CBA recipients at 30 days after transplantation displayed prolonged allograft survival (MSTs, 29 and 60 days, respectively). Cell proliferation, interleukin (IL)-2, and interferon-γ were suppressed in danazol-treated mice, whereas IL-4 and IL-10 were up-regulated. Moreover, danazol directly suppressed alloproliferation in mixed leukocyte cultures. Flow cytometry studies showed an increased CD4(+)CD25(+)Foxp3(+) cell population among splenocytes from danazol-treated mice. In conclusion, danazol induced prolonged cardiac allograft survival and generation of regulatory CD4(+) cells.

Aust N Z J Obstet Gynaecol.2012 Apr 30. doi: 10.1111/j.1479-828X.2012.01443.x. [Epub ahead of print]

Single incision laparoscopic surgery (SILS) in gynaecology: Feasibility and operative outcomes.

Behnia-Willison F, Foroughinia L, Sina M, McChesney P.


Obstetrics & Gynaecology, Flinders Medical Centre, Adelaide, South Australia, Australia.



Single incision laparoscopic surgery (SILS) represents the latest advancement in minimally invasive surgery, combining the benefits of conventional laparoscopic surgery, such as less pain and faster recovery, with improved cosmesis. Although the successful use of this technique is well reported in general surgery and urology, there is a lack of studies on SILS in gynaecology.


To evaluate the feasibility, safety, cosmesis and outcome of SILS in gynaecology.


A prospective case series analysis of 105 women scheduled to undergo surgery by SILS from August 2010 to November 2011. Intra-operative data such as operative time, estimated blood loss, complications, additional ports and hospital stay were collected. Post-operative pain and cosmetic outcomes (scar size) were also recorded.


Out of 105 women, SILS was performed for 84 (60 excisions of endometriosis, 13 divisions of adhesions, five hysterectomies, two mesh sacrohysteropexies and four ovarian cystectomies). SILS was not undertaken for 21 women because of a number of factors, including the lack of required equipment (eg bariatric scope, SILS port, roticulating instruments and diathermy leads). Four women required insertion of additional ports because of surgical difficulties. One intra-operative (uterine perforation) and seven post-operative complications (six wound infections and one vault haematoma) occurred. Mean operation times were as follows: mesh sacrohysteropexy – 60 min, excision of endometriosis – 55 min, hysterectomy – 150 min, laparoscopic division of adhesions – 62 min and ovarian cystectomy – 40 min.


Our experience shows that SILS is a feasible and safe technique for the surgical management of various gynaecological conditions. Satisfaction is high because of improved cosmesis and reduced analgesic requirements post-operatively.

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