Int J Mol Med. 2014 Apr;33(4):897-904.

DNA methylation patterns of steroid receptor genes ESR1, ESR2 and PGR in deep endometriosis compromising the rectum.

Meyer JL1Zimbardi D1Podgaec S2Amorim RL3Abrão MS2Rainho CA1.

 

Abstract

Endometriosis is characterized by the presence of endometrial-like tissue located outside the uterine cavity. Recent evidence suggests that endometriosis may be an epigenetic disease, as well as an estrogen-dependent disease. Based on the unique steroid hormone receptor expression profile observed in endometriotic lesions as compared to eutopic endometrium, the present study aimed to gain further insight into the DNA methylation patterns of alternative promoters of the steroid receptor genes ESR1, ESR2 and PGR in intestinal deep endometriosis, one of the most aggressive forms of endometriosis. The DNA methylation patterns were evaluated by methylation-specific polymerase chain reaction (MS-PCR) after bisulfite modification in 44 endometriotic tissues as well as in 7 matched eutopic endometrium. No differences in the DNA methylation were observed for the ESR1 and ESR2 genes. Methylation of the PGR gene was observed in 39% (17 out of 44) and 19% (7 out of 37) of the cases in the promoter regions B (PGRB) and A (PGRA), respectively. Both PGR promoter regions were methylated in 3 cases. PGRB methylated alleles were detected exclusively in the endometriotic lesions when compared to the eutopic endometrium obtained from the same patient. The effect of DNA methylation in inhibiting the PGR gene expression was corroborated by immuno-staining for PgR protein in a subset of tissue samples. The present study demonstrated that epigenetic changes occur in both promoter regions of the PGR gene in intestinal endometriosis. Since eutopic and ectopic tissues do not respond sufficiently to progesterone in women with endometriosis, further study is necessary to evaluate the effect of epigenetic alterations in progesterone-resistance in this enigmatic disease.

 

 

Eur J Nutr. 2014 Oct;53(7):1573-9

Coffee and caffeine intake and risk of endometriosis: a meta-analysis.

Chiaffarino F1Bravi FCipriani SParazzini FRicci EViganò PLa Vecchia C.

Abstract

PURPOSE:

The potential association between endometriosis and coffee/caffeine consumption has been analysed in several epidemiological studies. In order to establish whether caffeine influences the risk of endometriosis, we provide to summarize the evidence from published studies on this issue.

METHODS:

We performed a meta-analysis of epidemiological studies published up to January 2013. We computed summary relative risks (RR) of endometriosis for any, high and low versus no coffee/caffeine consumption.

RESULTS:

We identified a total eight studies, six case-control and two cohort studies, including a total of 1,407 women with endometriosis. The summary RR for any versus non-consumption were 1.26 [95% confidence interval (CI) 0.95-1.66] for caffeine and 1.13 (95% CI 0.46-2.76) for coffee consumption; the overall estimate was 1.18 (95% CI 0.92-1.49). The summary RR were 1.09 (95% CI 0.84-1.42) and 1.09 (95% CI 0.89-1.33) for high and low caffeine consumption as compared to no consumption, respectively.

CONCLUSION:

The present meta-analysis provided no evidence for an association between coffee/caffeine consumption and the risk of endometriosis. Coffee/caffeine consumption, as currently used in diet, does not carry a health risk.

 

 

J Obstet Gynaecol. 2014 May;34(4):336-40.

Laparoscopic treatment of endometriosis and effects on quality of life: a retrospective study using the short form EHP-5 endometriosis specific questionnaire.

Minas V1Dada T.

 

Abstract

Complete surgical eradication is considered the mainstay of treatment for endometriosis. The aim of the present study was to investigate patients’ own assessment of whether their laparoscopic treatment made a difference to their quality of life, as well as to assess local recurrence rates. We performed a retrospective analysis of 49 women who had laparoscopic treatment for endometriosis at our unit between 1 January 2008 and 1 January 2010. Patients were sent the Short Form EHP-5 questionnaire and asked to score their quality of life in relation to endometriosis symptoms, prior to the surgery and up to 48 months afterwards. Subgroup analysis of stage I/II and stage III/IV disease was performed as well as stratification of the period post-operation into 12-24, 25-36 and 37-48 months for follow-up analysis. Overall, the patients reported improvement in quality of life scores with a significant drop in mean scores from 46.9 pre- to 27.5 post-surgery, signifying benefits from the surgical intervention. All subgroups reported improvement in quality of life scores. The overall symptom recurrence rate was 18.3%. We conclude that patients, post-laparoscopic treatment of endometriosis, experience significant improvement in their quality of life, regardless of stage and this can be quantified and qualified.

Endocrinology. 2014 Apr;155(4):1489-97

Endometriosis impairs bone marrow-derived stem cell recruitment to the uterus whereas bazedoxifene treatment leads to endometriosis regression and improved uterine stem cell engraftment.

Sakr S1Naqvi HKomm BTaylor HS.

 

Abstract

Endometriosis is a disease defined by the ectopic growth of uterine endometrium. Stem cells contribute to the generation of endometriosis as well as to repair and regeneration of normal endometrium. Here we demonstrate that the selective estrogen receptor modulator bazedoxifene (BZA), administered with conjugated estrogens (CEs), leads to regression of endometriosis lesions as well as reduction in stem cell recruitment to the lesions. Female mice underwent transplantation of male bone marrow. Endometrium was transplanted in the peritoneal cavity of half to create experimental endometriosis. Mice with or without experimental endometriosis were randomized to BZA/CE or vehicle treatment. Endometriosis lesions, bone marrow-derived mesenchymal stem cell engraftment of the lesions, and eutopic endometrium as well as ovarian stimulation were assessed. BZA treatment significantly reduced lesion size, gland number, and expression of proliferation marker proliferating cell nuclear antigen. Ovarian weight was not affected. Stem cells were recruited to the endometriosis lesions, and this recruitment was dramatically reduced by BZA/CE treatment. Stem cell engraftment was reduced in the uterus of animals with endometriosis; however the number of stem cells engrafting the uterus was completely restored by treatment with BZA/CE. Competition between endometriosisand the eutopic endometrium for a limited supply of stem cells and depletion of normal stem cells flux to the uterus is a novel mechanism by which endometriosis interferes with endometrial function and fertility. BZA/CE not only treats lesions of endometriosis, it also dramatically reduces stem cell recruitment to the lesions and restores stem cell engraftment of the uterine endometrium.

 

 

Best Pract Res Clin Gastroenterol. 2014 Feb;28(1):53-67.

Multidisciplinary laparoscopic treatment for bowel endometriosis.

Wolthuis AM1Tomassetti C2.

 

Abstract

Endometriosis is a handicapping disease affecting young females in the reproductive period. It mainly occurs in the pelvis and affects the bowel in 3-37%. Endometriosis can cause menstrual and non-menstrual pelvic pain and infertility. Colorectal involvement results in alterations of bowel habit such as constipation, diarrhoea, tenesmus, and rarely rectal bleeding. A precise diagnosis about the presence, location and extent is necessary. Based on clinical examination, the diagnosis of bowel endometriosis can be made by transvaginal ultrasound, barium enema examination and magnetic resonance imaging. Multidisciplinary laparoscopic treatment has become the standard of care and depending on size of the lesion and site of involvement full-thickness disc excision or bowel resection is performed by an experienced colorectal surgeon. Anastomotic complications occur around 1%. Long-term outcome after bowel resection for severe endometriosis is good with a pregnancy rate of 50%.

 

 

Clin Obstet Gynecol. 2014 Mar;57(1):14-42.

Indications and alternatives to hysterectomy.

Solnik MJ1Munro MG.

 

Abstract

Hysterectomy remains one the most common procedures performed in North America. Because of a better understanding of a wide array of disease states and with emerging, more focused minimally invasive treatment options, a relative decline has been documented in the last several years. Although hysterectomy will ultimately eliminate all potential sources of abnormal uterine bleeding, various pharmacologic and surgical alternatives exist that may provide comparable benefit to the majority of women, especially if older than 40 years. Women experiencing chronic pelvic pain; however, should be counseled against hysterectomy until a more clear etiology has been identified.

 

 

West Afr J Med. 2013 Oct-Dec;32(4):302-6.

Thoracic endometriosis syndrome.

Tettey M1Edwin FAniteye ESeffah JTamatey MOfosu-Appiah EAdzamli IFrimpong-Boateng K.

Abstract

BACKGROUND:

Thoracic endometriosis syndrome is a rare constellation of different pathological entities arising from intrathoracic endometriosis. Reports from centers in Africa are scanty. Varying theories have been proposed but none satisfactorily explains the varying clinical manifestations.

OBJECTIVE:

To describe the demographics, pathological spectrum, and outcome of treatment of patients seen at a single centre in West Africa with intrathoracic endometriosis.

METHODS:

Twelve women who were seen at Ghana’s National Cardiotharacic Centre with intrathoracic endometriosis from 2004-2012 were retrospectively reviewed.

RESULTS:

The age range was from 24 – 39 years with a mean of 32 ± 5 years. Pelvic endometriosis was confirmed in 8 (66.7%) of the patients, 2 (16.7%) had ectopic endometrial tissue at the umbilicus and one (16.7%) had ectopic endometrial tissue at the mons pubis. Seven (58.3%) of the patients had undergone prior uterine surgery before the clinical onset of thoracic endometriosis. The right hemithorax was involved in all 12 (100%) patients studied. Pneumothorax was present in six (50%) women, hemothorax in five (41.7%) and hemopneumothorax in one (8.3%). Three of the four patients who benefited from video assisted thoracoscopy had abrasive pleurodesis followed by hormonal therapy. The rest of the patients had chemical pleurodesis with or without hormonal therapy.

CONCLUSION:

Thoracic endometriosis may be more prevalent in West Africa than previously believed. Outcome of treatment is satisfactory using a multidisciplinary approach.

 

 

Arch Gynecol Obstet. 2014 Jul;290(1):163-7.

Ovarian stripping versus cystectomy: recurrence of endometriosis and pregnancy rate.

Moscarini M1Milazzo GNAssorgi CPacchiarotti ACaserta D.

Abstract

PURPOSE:

To compare two different surgical techniques, stripping or cystectomy, in patients treated with the same post-operative medical therapy in terms of recurrence of endometrioma, recurrence of pain and spontaneous pregnancy rate within 2 years from surgery.

METHODS:

The inclusion criteria of this study were: (1) 25-40 years old; (2) ovarian endometrioma more than 3 cm of diameter detected by transvaginal ultrasonography (3) regular menstrual cycle (4) post-operative treatment with GnRH analogs, (5) tubal patency assessed by laparoscopic chromopertubation (6) normal human semen characteristics. Exclusion criteria were uterine myoma, previous medical treatment for endometriosis, presence of adenomyosis, previous surgery of ovarian endometrioma, multiple cysts, bilateral involvement, co-existence of deep endometriosis. Patients were assigned to two study groups: group A (N = 45) patients undergoing stripping technique and group B (N = 64) patients undergoing cystectomy technique for ovarian endometrioma.

RESULTS:

In group B the percentage of ultrasonographic recurrence (15.4 %, N = 15) is much lower than in group A (55.6 %, N = 25). (p value 0.001). In group B the percentage of symptomatic recurrence (21.8 %, N = 14) is much lower than in group A (53.3 %, N = 24) (p value 0.001). Spontaneous pregnancy rate in group A patients was of 4.4 % (N = 2) and in group B 22.3 % (N = 21), (p value 0.0072). However, the percentage of specimen with adjacent healthy ovarian tissue was lower in group A (26.6 %) than in group B (50 %) (p value 0.01).

CONCLUSIONS:

Among the different treatment options for surgical treatment of ovarian endometrioma, in our experience cystectomy appears to be the most appropriate treatment, both in terms of recurrence and pregnancy rate.

 

 

Arch Gynecol Obstet. 2014 Jul;290(1):75-82.

Copeptin is associated with the severity of endometriosis.

Tuten A1Kucur MImamoglu MKaya BAcikgoz ASYilmaz NOzturk ZOncul M.

Abstract

PURPOSE:

Endometriosis is defined as the presence of endometrial glands and stroma in ectopic locations and may be associated with local and systemic inflammatory processes. Copeptin is elevated in acute and chronic inflammation conditions. The aim of the present study was to determine whether serum copeptin levels were altered in women with endometriosis and played a role in the pathophysiology of the disease.

METHODS:

A total of 86 women were recruited for this case-control study. 50 patients with surgically proven endometriosis were included, while 36 patients without endometriosis comprised the control group. Patients were classified as having minimal, mild, moderate and severe disease in accordance with American Society of Reproductive Medicine revised classification. Two subgroups were formed by combining patients with minimal and mild disease and with moderate and severe disease (Stage 1-2, stage 3-4; respectively). Levels of copeptin, tumor markers (CA-125, CA-19-9, CA-15-3) and C-reactive protein in serum were measured.

RESULTS:

Serum copeptin, CA-125, CA-15-3 and CA-19-9 levels were higher in the endometriosis group (p: 0.002; 0.001; 0.017; 0.015; respectively). Copeptin and CA-19-9 levels were significantly higher in stage 3-4 group as compared to stage 1-2 group (p: 0.004; 0.036 respectively). Serum copeptin levels were positively correlated with stage of the disease and size of endometriomas. ROC analysis revealed that CA-125 had the highest AUC for predicting endometriosis (0.938; 95 % confidence interval 0.882-0.993; p: 0.001).

CONCLUSIONS:

Serum copeptin levels were significantly higher in patients with endometriosis as compared to healthy controls. Moreover, severity of the disease was correlated with serum copeptin levels.

 

 

 

Am J Transl Res. 2014 Jan 15;6(2):104-13.

The elusive and controversial roles of estrogen and progesterone receptors in human endometriosis.

Shao R1Cao S2Wang X3Feng Y4Billig H1.

 

Abstract

Endometriosis is a complex and challenging disease that involves aberrant adhesion, growth, and progression of endometrial tissues outside of the uterine cavity, and there is evidence to suggest that estrogen plays a key role in its development and progression. Numerous in vivo clinical studies have described the ectopic expression and regulation of estrogen receptor (ER) and progesterone receptor (PR) in the different types of endometriosis compared to normal or eutopic endometrium. However, we have noticed that conflicting and contradictory results have been presented in terms of ER subtype (ERα and ERβ) and PR isoform (PRA and PRB) expression. Both ER and PR are transcription factors and ER/PR-mediated responses depend on the coordinated, opposing, and compensatory functions of ER subtypes and PR isoforms. Moreover, analysis of the uterine phenotypes of ERα/ERβ and PRA/PRB knockout mice indicates that different ER subtypes and PR isoforms mediate distinct responses to steroid hormones and play different roles in uterine function. In this review, we outline studies that have elucidated the molecules and signaling pathways that are linked to ER and/or PR signaling pathways in the development and progression of endometriosis.

 

 

Hum Reprod. 2014 Apr;29(4):670-6.

Does ovarian suspension following laparoscopic surgery for endometriosisreduce postoperative adhesions? An RCT.

Hoo WL1Stavroulis APateman KSaridogan ECutner APandis GTong ENJurkovic D.

Abstract

STUDY QUESTION:

Is temporary ovarian suspension following laparoscopic surgery for severe pelvic endometriosis an effective method for reducing the prevalence of postoperative ovarian adhesions?

SUMMARY ANSWER:

Temporary ovarian suspension for 36-48 h following laparoscopic treatment of severe endometriosis does not result in a significant reduction of postoperative ovarian adhesions.

WHAT IS KNOWN ALREADY:

Pelvic adhesions often develop following laparoscopic surgery for severe pelvic endometriosis. Adhesions can cause chronic pelvic pain and fertility problems compromising the success of treatment. Small observational studies suggested that temporary postoperative ovarian suspension to the abdominal wall may significantly reduce the prevalence of postoperative ovarian adhesions.

STUDY DESIGN, SIZE, DURATION:

This was a prospective within group comparison double-blind RCT. We recruited premenopausal women with severe pelvic endometriosis who required extensive laparoscopic surgery with preservation of the uterus and ovaries. Severity of the disease and eligibility for inclusion were determined at surgery. A total of 55 women were randomized to unilateral ovarian suspension for 36-48 h, 52 of which were included in the final analysis. Both ovaries were routinely suspended to the anterior abdominal wall during surgery. At the end of the operation, each woman was randomized to having only one ovary suspended postoperatively. The suture suspending the contralateral ovary was cut and a new transabdominal suture was inserted to act as a placebo. Both sutures were removed 36-48 h after surgery prior to discharge. Three months after surgery, all women attended for a detailed transvaginal ultrasound scan to assess ovarian mobility. Both the women and the ultrasound operators were blinded as to the side of postoperative ovarian suspension. The primary outcome was the prevalence of ovarian adhesions as described on ultrasound examination. Secondary outcomes were the severity of adhesions and the presence and intensity of postoperative pain.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

All 55 participants had severe pelvic endometriosisconfirmed at laparoscopy. As each participant had only one of their ovaries suspended at the end of surgery, they acted as their own control.

MAIN RESULTS AND THE ROLE OF CHANCE:

The median interval between ovarian suspension and postoperative scan was 99 days (interquartile range 68-114). There was no significant difference (P = 0.23) in the prevalence of postoperative ovarian adhesions between the suspended (20/52) and unsuspended (27/52) side (38.5 versus 51.9%) [odds ratio 0.56 (95% confidence interval 0.22-1.35)].

LIMITATIONS, REASONS FOR CAUTION:

Ovaries were suspended postoperatively for 36-48 h. Longer suspension could result in lower prevalence of postoperative adhesions.

WIDER IMPLICATIONS OF THE FINDINGS:

The value of temporary ovarian suspension in women having surgery for mild-to-moderate endometriosis should be investigated further. The potential benefits of other adhesion prevention strategies, such as surgical barrier agents, in women undergoing surgical treatment for severe pelvic endometriosis should also be explored.

STUDY FUNDING/COMPETING INTERESTS:

E.S. received honoraria from Ethicon for provision of training to healthcare professionals and consultancy fees from Bayer. W.H. was supported by the research fund provided by the Gynaecology Ultrasound Centre, London UK. A.C. is on the advisory board for surgical innovations for which he receives an annual honorarium. A.C. also received support for courses and education from Storz and Johnson and Johnson and support for clinical nursing from Covidien and Lotus. The other authors declared no competing interests.

 

 

Hum Pathol. 2014 Apr;45(4):761-7.

Endometrial cysts within the liver: a rare entity and its differential diagnosis with mucinous cystic neoplasms of the liver.

Hsu M1Terris B2Wu TT3Zen Y4Eng HL5Huang WT5Yeh MM6.

 

Abstract

Endometrial cysts within the liver are rare but can present as diagnostic challenges on small biopsies or frozen sections and may mimic mucinous cystic neoplasms (MCN) of the liver. Five cases of endometrial cysts and 6 cases of MCNs within the liver were collected. The clinicopathological, imaging, and immunohistochemical features were systematically reviewed and compared. The average size of the endometrial cysts was 8.3 cm. Four patients had a prior pelvic operation and coexisting endometriosis at other sites. All 5 cases of endometrial cysts had positive ER staining within both the epithelium and the stroma. PR was also positive in both epithelial and stromal cells in 4 cases. Four cases had additional immunostains performed, which all showed cytokeratin 19 and cytokeratin 7 positivity (only in epithelium) and CD10 positivity (only in stroma). α-Inhibin and calretinin were negative for both the epithelium and the stroma in all 4 cases. All 6 MCN cases (mean size, 11.1 cm) had positive ER, PR, and α-inhibin staining only in the stroma. ER and PR were positive in both the epithelium and stromal cells in endometrial cysts, whereas they were positive only in the stromal cells of MCNs. The stromal cells were CD10 positive and α-inhibin negative in endometrial cysts as opposed to the opposite staining pattern in MCNs. Awareness of this distinct staining pattern and the possibility of endometrial cysts in the liver can lead to accurate diagnoses and appropriate treatment modalities.

 

Eur J Pharmacol. 2014 Mar 15;727:140-7.

Dinitrosyl iron complexes with glutathione suppress experimental endometriosis in rats.

Burgova EN1Tkachev NА1Adamyan LV2Mikoyan VD1Paklina OV3Stepanyan AA2Vanin AF4.

 

Abstract

Dinitrosyl iron complexes (DNIC) with glutathione exert a cytotoxic effect on endometrioid tumours in rats with surgically induced experimental endometriosis. Intraperitoneal treatment of rats (Group 1) with DNIC (12.5μmoles/kg, daily, for 12 days), beginning with day 4 after the surgical operation (implantation of two 2mm-thick uterine fragments onto the abdominal wall) followed by 14-day keeping of animals on a standard feeding schedule (without medication) resulted in complete inhibition of the growth of endometrioid implants (EMI) in the majority of experimental animals. The ratio of mean EMI volumes in control and experimental rats of Group 1 was 14:1. In Group 2 rats, the use of a similar treatment protocol 4 weeks after surgery changed this ratio to 1.4:1. Noteworthy, the decrease of this ratio was irrelevant to deceleration of EMI growth at later periods after surgery. The histopathological analysis of EMI samples from experimental rats of Group 2 demonstrated complete disappearance of endometrial cysts suggesting a cytotoxic effect of DNIC on the tumours. The data obtained demonstrate that DNIC with glutathione and, probably, with other thiol-containing ligands hold considerable promise in the design of drugs for treating endometriosis in female patients.

Am J Reprod Immunol. 2014 Apr;71(4):359-67.

Expression of natural cytotoxicity receptors on peritoneal fluid natural killer cell and cytokine production by peritoneal fluid natural killer cell in women with endometriosis.

Funamizu A1Fukui AKamoi MFuchinoue KYokota MFukuhara RMizunuma H.

Abstract

PROBLEM:

To investigate the relationship between the expression of natural cytotoxicity receptors (NCRs) on peritoneal fluid (PF) natural killer (NK) (pfNK) cells and cytokine production by pfNK cells in women with endometriosis.

METHOD OF STUDY:

Peritoneal fluid was collected from women with endometriosis undergoing laparoscopic surgery (n = 21) and controls without endometriosis (n = 28). The expression of NK cell surface antigens such as CD16 and NCRs (NKp46, NKp44 and NKp30) on pfNK cells, and cytokines production by pfNK cells [tumor necrosis factor (TNF)-α, IFN-γ, IL-4, IL-10, GM-CSF and transforming growth factor (TGF)-β1] were measured using multicolor flow cytometry.

RESULTS:

The percentages of CD56(+)/NKp46(+) cells and CD56(dim) /NKp46(+) cells in severe endometriosis group were significantly lower than that in controls. TNF-α and IFN-γ production by pfNK cells in severe endometriosis group was significantly higher than those in controls.

CONCLUSION:

The differential expression of NKp46, TNF-α, and IFN-γ on pfNK cells in women with severe endometriosis may allow the proliferation and angiogenesis of endometriotic cells.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Apr;175:172-7.

Experimental endometriosis remission in rats treated with Achillea biebersteinii Afan.: histopathological evaluation and determination of cytokine levels.

Demirel MA1Suntar I2Ilhan M2Keles H3Kupeli Akkol E4.

Abstract

OBJECTIVE:

The aim of the present study is to assess the beneficial effects of Achillea biebersteinii Afan. in the treatment of endometriosis in order to find scientific evidence for the folkloric use of this plant.

STUDY DESIGN:

Experimental endometriosis was induced in six-week-old female, nonpregnant, Sprague Dawley rats by suturing a 15mm piece of endometrium from uterine cornu into abdominal wall. After twenty-eight days, a second laparotomy was performed: the endometrial foci areas were measured and intra-abdominal adhesions were scored, and the abdomen was closed. Different groups then received n-hexane, ethyl acetate (EtOAc) and methanol (MeOH) extracts prepared from the aerial parts of A. biebersteinii, and a control group received inert material, administered per os once a day throughout the experiment. At the end of the treatment procedure all rats were sacrified and endometriotic foci areas and intra-abdominal adhesions were again evaluated and compared with the previous findings. The tissues were also histopathologically investigated. Moreover, peritoneal fluid was collected to detect tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) levels. Dunnett’s test was used to determine the significance of differences between groups. In order to compare two groups Student’s t test was used.

RESULTS:

Post-treatment volumes of endometrial foci were found to be significantly decreased, and no adhesion was detected, in the EtOAc extract treated group. The levels of TNF-α, VEGF and IL-6 also fell after the treatment with EtOAc extract. The therapeutic effect of the EtOAc extract of A. biebersteinii could be attributed to the flavonoid aglycones found in the extract.

CONCLUSION:

The EtOAc extract of A. biebersteinii appears to be a promising alternative for the treatment of endometriosis.

 

 

Am J Obstet Gynecol. 2014 Jun;210(6):531.e1-8.

ENMD-1068, a protease-activated receptor 2 antagonist, inhibits the development of endometriosis in a mouse model.

Wang Y1Lin M2Weng H3Wang X1Yang L2Liu F4.

Abstract

OBJECTIVE:

Protease-activated receptor 2 plays an important role in the pathogenesis of endometriosis. We studied the effect of ENMD-1068, a protease-activated receptor 2 antagonist, on the development of endometriosis in a noninvasive fluorescent mouse model.

STUDY DESIGN:

A red fluorescent protein-expressing xenograft model of human endometriosis was created in nude mice. After endometriosis induction, the mice were injected intraperitoneally with either 25 mg/kg or 50 mg/kg ENMD-1068 or with 200 μL of the vehicle control daily for 5 days. The endometriotic lesions that developed in the mice were then counted, measured, and collected. The lesions were assessed for the production of interleukin 6 and monocyte chemotactic protein-1 by enzyme-linked immunosorbent assays and evaluated for the activation of nuclear factor-κB and the expression of vascular endothelial growth factor by immunohistochemical analyses. Cell proliferation and apoptosis were assessed by immunohistochemistry for Ki-67 and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, respectively.

RESULTS:

ENMD-1068 dose-dependently inhibited the development of endometriotic lesions (P < .05) without apparent toxicity to various organs of the treated mice. Consistently, ENMD-1068 dose-dependently inhibited the expression of interleukin 6 and nuclear factor-κB (P < .05) and cell proliferation (P < .05) in the lesions, as well as increased the percentage of apoptotic cells (P < .05). ENMD-1068 reduced the levels of monocyte chemotactic protein-1 and vascular endothelial growth factor in the lesions (P < .05), but not in a dose-dependent manner.

CONCLUSION:

Our study suggests that ENMD-1068 is effective in suppressing the growth of endometriosis, which might be attributed to the drug’s antiangiogenic and antiinflammatory activities.

 

 

Zhonghua Fu Chan Ke Za Zhi. 2013 Dec;48(12):907-10.

Study on microRNA expression in endometrium of luteal phase and its relationship with infertility of endometriosis.

Ruan Y1Qian WP2Zhang CH1Zhou L1Hou ZH1.

Abstract

OBJECTIVE:

To study the different expression of microRNA(miRNA) including mir-29c, mir-200a, mir-145 in the mid-secretary endometrium and its relationship with infertility of endometriosis.

METHODS:

From August 2011 to February 2013, 36 infertile cases with endometriosis confirmed by laparoscopy and pathology and excluded the other infertile factors in Department of Reproductive Medicine in Peking University Shenzhen Hospital were enrolled in this study, which were divided into 17 cases with stage I-II, 19 cases with stage III-IV according to the revised classification American Fertility Society. Forty-four healthy women with male factor infertility were chosen as control group. The relative expression levels of mir-29c, mir-200a, mir-145 in the endometrium of women in two groups were detected by using real-time quantitative polymerase chain reaction. Those women were followed up for pregnancy outcome of endometriosis group after assisted reproductive techniques (pregnancy and non-pregnancy group respectively).

RESULTS:

(1) The expression of miRNA between endometriosis and control groups:the average expression level of mir-29c, mir-200a, mir-145 in the endometrium of endometriosis group was 2.46 ± 1.98, 3.20 ± 2.45, 6.378 ± 3.275, which were significantly higher than 1.36 ± 1.05, 2.04 ± 1.16, 4.548 ± 1.885 in control group (P = 0.026, 0.027, 0.041, respectively). (2) The expression of miRNA between I-II stage and III-IV: the average expression level of mir-29c, mir-200a, mir-145 in the endometrium was 0.53 ± 0.51, 0.33 ± 0.26, 0.048 ± 0.021 in patients with of stage I-II, while 0.26 ± 0.18, 0.28 ± 0.12, 0.045 ± 0.016 in stage III-IV respectively, there were no statistically significant differences between the two groups (P = 0.191,0.661,0.753, respectively) . (3) The expression of miRNA between pregnancy and non-pregnancy groups:the average expression level of mir-29c, mir-200a, mir-145 in the endometrium were 0.60 ± 0.30, 1.23 ± 0.48, 0.886 ± 0.238 in pregnancy group, while 2.64 ± 1.73, 4.39 ± 2.58, 7.199 ± 3.945 in non pregnancy group, there were statistically significant differences between the two groups (P = 0.030,0.039,0.028, respectively).

CONCLUSION:

Up-regulation of mir-29c, mir-200a, mir-145 in the endometrial tissue might play a role in endometriosis associated infertility.

 

 

 

Ultrasound Obstet Gynecol. 2014 Sep;44(3):354-60

Imaging in gynecological disease. 10: Clinical and ultrasound characteristics of decidualized endometriomas surgically removed during pregnancy.

Mascilini F1Moruzzi CGiansiracusa CGuastafierro FSavelli LDe Meis LEpstein ETimor-Tritsch IEMailath-Pokorny MErcoli AExacoustos CBenacerraf BRValentin LTesta AC.

Abstract

OBJECTIVES:

To describe the clinical history and ultrasound findings in women with decidualized endometriomas surgically removed during pregnancy.

METHODS:

In this retrospective study, women with a histological diagnosis of decidualized endometrioma during pregnancy who had undergone preoperative ultrasound examination were identified from the databases of seven ultrasound centers. The ultrasound appearance of the tumors was described on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) by one author from each center using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, two authors reviewed together available digital ultrasound images and used pattern recognition to describe the typical ultrasound appearance of decidualized endometriomas.

RESULTS:

Eighteen eligible women were identified. Median age was 34 (range, 20-43) years. Median gestational age at surgical removal of the decidualized endometrioma was 18 (range, 11-41) weeks. Seventeen women (94%) were asymptomatic and one presented with pelvic pain. In three of the 18 women an ultrasound diagnosis of endometrioma had been made before pregnancy. The original ultrasound examiner was uncertain whether the mass was benign or malignant in 10 (56%) women and suggested a diagnosis of benignity in nine (50%) women, borderline in eight women (44%), and invasive malignancy in one (6%) woman. Seventeen decidualized endometriomas contained a papillary projection, and in 16 of these at least one of the papillary projections was vascularized at power or color Doppler examination. The number of cyst locules varied between one (n = 11) and four. No woman had ascites. When using pattern recognition, most decidualized endometriomas (14/17, 82%) were described as manifesting vascularized rounded papillary projections with a smooth contour in an ovarian cyst with one or a few cyst locules and ground-glass or low-level echogenicity of the cyst fluid.

CONCLUSIONS:

Rounded vascularized papillary projections with smooth contours within an ovarian cyst with cyst contents of ground-glass or low-level echogenicity are typical of surgically removed decidualized endometriomas in pregnant women, most of whom are asymptomatic.

 

 

Sci Transl Med. 2014 Feb 5;6(222):222ra16.

Molecular network analysis of endometriosis reveals a role for c-Jun-regulated macrophage activation.

Beste MT1Pfäffle-Doyle NPrentice EAMorris SNLauffenburger DAIsaacson KBGriffith LG.

 

Abstract

Clinical management of endometriosis is limited by the complex relationship between symptom severity, heterogeneous surgical presentation, and variability in clinical outcomes. As a complement to visual classification schemes, molecular profiles of disease activity may improve risk stratification to better inform treatment decisions and identify new approaches to targeted treatment. We use a network analysis of information flow within and between inflammatory cells to discern consensus behaviors characterizing patient subpopulations. Unsupervised multivariate analysis of cytokine profiles quantified by multiplex immunoassays identified a subset of patients with a shared “consensus signature” of 13 elevated cytokines that was associated with common clinical features of endometriosis, but was not observed among patient subpopulations defined by morphologic presentation alone. Enrichment analysis of consensus markers reinforced the primacy of peritoneal macrophage infiltration and activation, which was demonstrably elevated in ex vivo cultures. Although familiar targets of the nuclear factor κB family emerged among overrepresented transcriptional binding sites for consensus markers, our analysis provides evidence for an unexpected contribution from c-Jun, c-Fos, and AP-1 effectors of mitogen-associated kinase signaling. Their crucial involvement in propagation of macrophage-driven inflammatory networks was confirmed via targeted inhibition of upstream kinases. Collectively, these analyses suggest a clinically relevant inflammatory network that may serve as an objective measure for guiding treatment decisions for endometriosis management, and in the future may provide a mechanistic endpoint for assessing efficacy of new agents aimed at curtailing inflammatory mechanisms that drive disease progression.

 

 

J Minim Access Surg. 2014 Jan;10(1):27-33.

Laparoscopic management of moderate: Severe endometriosis.

Shah PR1Adlakha A1.

Abstract

OBJECTIVES:

To assess the feasibility of laparoscopic surgery in cases of moderate-severe endometriosis.

MATERIALS AND METHODS:

A prospective study was carried out in a tertiary centre over a period of 2 years. Moderate to severe endometriosis was defined by revised American fertility society (rAFS) classification (41 patients). Various procedures were done to provide symptomatic relief. Feasibility of laparoscopic surgery and various patient parameters were analysed.

RESULTS:

Various procedures like adhesiolysis in POD, excision of endometriomas, resection of endometriotic nodules in the recto-vaginal septum, ureterolysis and total laparoscopic hysterectomy with/ without oophorectomy were done. Majority of patients underwent cystectomy for endometriomas (53.6%) or adhesiolysis with excision of endometriotic nodule (36.5%). Total laparoscopic hysterectomy with or without ooperectomy was done in 31.7% patients. Of the total 9 patients with primary infertility and moderate-severe endometriosis, 5 patients (55.5%) conceived after surgery.

CONCLUSION:

There is good evidence that in experienced hands laparoscopic surgery helps in long-term symptomatic relief, improves pregnancy rates and reduces recurrence of disease with largely avoiding complications.

 

 

Akush Ginekol (Sofiia). 2013;52(6):38-42.

Endometriosis and endometriosis-related ovarian neoplasms.

Totev TTomov SGorchev G.

 

Abstract

Endometriosis is an estrogen-dependent, chronic gynecological disorder. Although endometriosis is a benign lesion, it shares several common characteristics with invasive cancer. Numerous epidemiologic studies indicate, that endometriosis patients have an increased risk of clear cell and endometrioid ovarian cancer. There is an intermediary lesion between endometriosis and malignant neoplasms – “atypical endometriosis”. Genetic factors play a role in the malignant transformation through pathways related to oxidative stress, inflammation and hyperestrogenism.

 

 

J Ovarian Res. 2014 Feb 6;7:17.

Novel three-dimensional in vitro models of ovarian endometriosis.

Brueggmann DTempleman CStarzinski-Powitz ARao NPGayther SA1Lawrenson K.

Abstract

BACKGROUND:

Endometriosis is characterized by the presence of functional endometrial tissue outside of the uterine cavity. It affects 1 in 10 women of reproductive age. This chronic condition commonly leads to consequences such as pelvic pain, dysmenorrhea, infertility and an elevated risk of epithelial ovarian cancer. Despite the prevalence of endometriosis and its impact on women’s lives, there are relatively few in vitro and in vivo models available for studying the complex disease biology, pathophysiology, and for use in the preclinical development of novel therapies. The goal of this study was to develop a novel three-dimensional (3D) cell culture model of ovarian endometriosis and to test whether it is more reflective of endometriosis biology than traditional two dimensional (2D) monolayer cultures.

METHODS:

A novel ovarian endometriosis epithelial cell line (EEC16) was isolated from a 34-year old female with severe endometriosis. After characterization of cells using in vitro assays, western blotting and RNA-sequencing, this cell line and a second, already well characterized endometriosis cell line, EEC12Z, were established as in vitro 3D spheroid models. We compared biological features of 3D spheroids to 2D cultures and human endometriosis lesions using immunohistochemistry and real-time semi-quantitative PCR.

RESULTS:

In comparison to normal ovarian epithelial cells, EEC16 displayed features of neoplastic transformation in in vitro assays. When cultured in 3D, EEC16 and EEC12Z showed differential expression of endometriosis-associated genes compared to 2D monolayer cultures, and more closely mimicked the molecular and histological features of human endometriosis lesions.

CONCLUSIONS:

To our knowledge, this represents the first report of an in vitro spheroid model of endometriosis. 3D endometriosis models represent valuable experimental tools for studying EEC biology and the development of novel therapeutic approaches.

 

 

Fertil Steril. 2014 Apr;101(4):1038-46.e7.

Genome-wide profiling of long noncoding ribonucleic acid expression patterns in ovarian endometriosis by microarray.

Sun PR1Jia SZ1Lin H1Leng JH2Lang JH1.

Abstract

OBJECTIVE:

To profile the long noncoding RNA (lncRNA) expression patterns in ovarian ectopic endometrial tissue compared with paired eutopic endometrial tissue.

DESIGN:

Genome-wide expression analysis of human tissue.

SETTING:

University hospital.

PATIENT(S):

Twenty-five patients receiving laparoscopic surgeries for ovarian endometriosis.

INTERVENTION(S):

Ovarian ectopic endometrial tissue was obtained during surgery. Eutopic endometrial tissue was taken by curettage at the same time.

MAIN OUTCOME MEASURE(S):

Ectopic and eutopic endometrial lncRNA and messenger RNA (mRNA) expression levels were determined by microarray in four patients; quantitative reverse transcription-polymerase chain reaction validation of 10 differentially expressed lncRNAs was conducted in another 21 patients. The lncRNAs’ functions were predicted through coexpressed mRNA annotations.

RESULT(S):

A total of 948 lncRNA transcripts and 4,088 mRNA transcripts were dysregulated in ectopic endometrial tissue, compared with paired eutopic endometrial tissue. The expressions of the 10 chosen lncRNAs were validated by quantitative reverse transcription-polymerase chain reaction. Functional analysis suggests that several groups of lncRNAs may participate in biological pathways related to endometriosis by cis- and/or trans-regulation of protein-coding genes.

CONCLUSION(S):

This study constitutes the first report of lncRNA expression patterns in human ectopic and eutopic endometrial tissue. Nearly 1,000 dysregulated lncRNA transcripts are found by microarray.

 

 

Fertil Steril. 2014 Apr;101(4):1031-7.

Enhanced follicular recruitment and atresia in cortex derived from ovaries with endometriomas.

Kitajima M1Dolmans MM2Donnez O3Masuzaki H4Soares M3Donnez J5.

Abstract

OBJECTIVE:

To evaluate the effects of endometriomas on the regulation of early follicular development.

DESIGN:

Histologic analysis of prospectively collected biopsy samples.

SETTING:

Research unit in a university hospital.

PATIENT(S):

Women <40 years of age who have ovarian endometriomas.

INTERVENTION(S):

Biopsy of healthy cortex from ovaries affected by endometriomas (≤ 4 cm) and contralateral ovaries without cysts.

MAIN OUTCOME MEASURE(S):

Histomorphological staging of early follicles, measurement of follicle, oocyte, and oocyte nucleus diameters, immunohistochemistry of proliferating cell nuclear antigen, and caspase-3.

RESULT(S):

Thirteen cortical samples from ovaries with endometriomas and 13 samples from contralateral ovaries without endometriomas were evaluated. Cortex from ovaries with endometriomas contained significantly more morphologically atretic early follicles than cortex from contralateral ovaries without cysts. These follicles showed cleaved caspase-3 immunostaining. Diameters of primordial follicles and oocytes were decreased in cortex from ovaries with endometriomas, whereas early follicles with proliferating cell nuclear antigen-positive granulosa cells (GCs) were significantly increased in number.

CONCLUSION(S):

Ovaries with endometriomas, which may be more prone to local pelvic inflammation, showed activated follicular recruitment and atresia of early follicles. The potential contribution of inflammation to follicle “burnout” in case of endometriomas is discussed.

 

 

Gynecol Obstet Invest. 2014;77(2):104-10.

Clinical characteristics of patients in Japan with ovarian cancer presumably arising from ovarian endometrioma.

Taniguchi F1Harada TKobayashi HHayashi KMomoeda MTerakawa N.

Abstract

OBJECTIVE:

To investigate the clinical features of patients in Japan with malignant transformation of ovarian endometrioma.

PATIENTS:

Thirty-three patients diagnosed with ovarian cancer presumably arising from endometrioma were recruited retrospectively. These patients had been followed for at least 2 years after the ovarian endometrioma diagnosis, then continued to be followed after they had been found to have malignant transformation.

RESULTS:

The average age of the patients was 47.7 ± 9.3 years; 75.7% were premenopausal at the time of diagnosis of ovarian cancer. Among the 33 patients, ovarian cancer developed in the ipsilateral ovary of 6 patients with endometrioma after cystectomy. Twenty-eight patients were diagnosed with stage I ovarian cancer, and major histotypes were clear cell in 23 cases and endometrioid in 8. Before surgery for cancer, mural nodules within the endometriomas were detected in 32 patients, and 1 patient had a small 3-mm nodule. In 30 patients, the diameter of the tumor doubled in size 6 months prior to the diagnosis of malignant transformation. The diameter of the endometrioma and the preoperative CA125 value did not significantly correlate.

CONCLUSIONS:

To detect malignant transformation of ovarian endometrioma early and precisely, the clinician should determine the existence of a mural nodule and assess the rapid growth of the endometrioma.

 

Ginekol Pol. 2013 Dec;84(12):1041-4.

Reproductive outcome after surgical treatment of endometriosis–retrospective analytical study.

Cirpan T1Akman L1Yucebilgin MS1Terek MC1Kazandi M1.

Abstract

OBJECTIVE:

The aim of the study was to investigate the reproductive outcomes of patients after surgical treatment of endometriosis.

MATERIAL AND METHODS:

The study included 100 infertile women, aged 21 to 41 years, who underwent surgical treatment of endometriosis. From January 2007 to January 2012, excision of endometriosis was performed by operative laparoscopy or laparotomy Demographic, clinical, surgical and reproductive outcomes of 52 patients were retrospectively analyzed.

RESULT:

Twenty-three pregnancies (44%) were obtained in 52 patients, resulting in 16 term pregnancies, 4 spontaneous abortions under 16 weeks gestation, 2 spontaneous abortions at 20 gestational weeks and 1 ectopic pregnancy Twenty nine patients did not achieve pregnancy and 68.9% (20/29) of them were treated with IVF-ICSI. Spontaneous pregnancies were obtained within 7 months after the surgery whereas IVF-ICSI pregnancies were obtained within the period of 11 months. Seven patients were stage 1, 14 patients stage II, 19 patients stage III, and 12 patients stage IV according to the American Fertility Society (AFS) Classification of Endometriosis. The pregnancy rate was 57% in stages I-II, 47% in stage III, 16% in stage IV endometriosis; and the rate of term pregnancies was 83%, 66%, and 0%, respectively Seven pregnancies (7/14) were obtained in patients with bilateral endometriosis and 5 of them resulted in term pregnancy Sixteen pregnancies (16/38) were obtained in patients with unilateral endometriosis and 11 of them resulted in term pregnancy

CONCLUSION:

After surgical treatment of endometriosis, the pregnancy and live birth rates seem to be improved. Reproductive outcome is closely associated with the AFS score. Bilaterality of endometriosis does not affect pregnancy outcome.

 

 

J Endometr. 2013 Jan 1;5(1):17-26.

A prospective cohort study of Vitamins B, C, E, and multivitamin intake and endometriosis.

Darling AM1Chavarro JE2Malspeis S3Harris HR4Missmer SA5.

Abstract

PURPOSE:

Diet is a potentially modifiable risk factor for endometriosis. It has been hypothesized that vitamins C, E, and the B vitamins may influence factors involved in the pathogenesis of endometriosis, such as oxidative stress and steroid hormone metabolism. In this large, prospective cohort study, we examined the relation between intake of vitamins C, E, the B vitamins, and the use of multivitamin supplements and diagnosis of endometriosis.

METHODS:

Data were collected from women in the Nurses’ Health Study II between 1991 and 2005. Diet was assessed via food frequency questionnaire. Incidence rate ratios (RR) and 95% confidence intervals (CI) were estimated using time-varying Cox proportional hazards models.

RESULTS:

A total of 1383 incident cases of laparoscopically-confirmed endometriosis were observed among 70,617 women during 735,286 person years of follow-up. Intakes of thiamine (B1) (RR = 0.84, CI = 0.72-0.99; P-value, test for linear trend [P] = 0.04), folate (B9) (RR = 0.79, CI = 0.66-0.93; P = 0.003), vitamin C (RR = 0.81, CI = 0.68-0.95; P = 0.02), and vitamin E (RR = 0.70, CI = 0.59-0.83; P<0.0001) solely from food sources were inversely related to endometriosis diagnosis. However, intakes of these nutrients from supplements alone were unrelated to endometriosis.

CONCLUSION:

Thiamine, folate, vitamin C, and vitamin E from food sources are inversely related to endometriosis risk. Our results suggest that the protective mechanism may not be related to the nutrients themselves but rather other components of foods rich in these micronutrients or factors correlated with diets high in these vitamin-rich foods.

Gynecol Obstet Invest. 2014;77(2):117-20.

Lateralization of ovarian follicles.

AlSerri A1Kuriya AHolzer HTulandi T.

Abstract

BACKGROUND/AIM:

To evaluate a possible lateralization of antral follicle count (AFC) based on the finding that endometriosis, if present, is more commonly found in the left hemipelvis.

METHODS:

We evaluated the records of 6,617 baseline ultrasounds conducted at our Reproductive Center between 2007 and 2011 in a university teaching hospital setting. We included all ultrasounds with an AFC of 1 or greater and excluded those with incomplete documentation or with ovarian cyst, including endometriotic cysts (n = 909). The main outcome measure was the comparison of the number of antral follicles between the right and left ovary.

RESULTS:

The number of antral follicles in the right ovary (median 18, range 15-22) was significantly higher than in the left ovary (median 16, range 13-20) among women with polycystic ovaries (PCO, AFC ≥24). Similarly, the number of antral follicles in the right ovary (median 8, range 6-10) was significantly higher than in the left ovary (median 7, range 5-9) in women with no PCO but normal ovarian reserve (AFC 10-23).

CONCLUSIONS:

In women with PCO and non-PCO with normal ovarian reserve, the right ovary contains a higher number of antral follicles than the left ovary.

 

 

Case Rep Dermatol. 2013 Dec 21;5(3):368-72

Spontaneous cutaneous endometriosis of the umbilicus.

Gin TJ1Gin AD1Gin D2Pham A3Cahill J2.

 

Abstract

Cutaneous endometriosis that arises de novo, without a prior history of surgery, is a rare phenomenon. The clinical diagnosis of cutaneous endometriosis remains challenging due to the variable clinical appearance and symptoms of the condition, and therefore must be considered in the differential diagnosis of any umbilical lesion. We report a 31-year-old woman who presented with spontaneous cutaneous endometriosis of the umbilicus.

 

 

 

Iran Biomed J. 2014;18(2):60-6.

Effect of myomectomy on endometrial glutathione peroxidase 3 (GPx3) and glycodelin mRNA expression at the time of the implantation window.

Farimani Sanoee M1Alizamir T2Faramarzi S3Saidijam M4Yadegarazari R4Shabab N4Rastgoo Haghi A5Alizadeh Z1.

Abstract

BACKGROUND:

In fertile women, glycodelin and glutathione peroxidase 3 (GPx3) genes expression rises during the luteal phase, with a peak occurring during the implantation window. The expression of these genes decreases in women with myomas. To determine whether myomectomy would reverse glycodelin and GPx3 expression, we evaluated the transcript levels of these genes in the endometrium of patients before and after myomectomy.

METHODS:

Expression of glycodelin and GPx3 genes were examined prospectively during the midluteal phase in the endometrium obtained from infertile women with myoma (n = 12) before and three months after myomectomy. Endometrial expression of these genes was evaluated using quantitative real-time RT-PCR.

RESULTS:

Endometrial glycodelin mRNA expression levels (normalized to 18S rRNA expression) were increased significantly in endometrium of patients after myomectomy (P = 0.02). GPx3 mRNA expression was increased insignificantly after myomectomy (P = 0.43).

CONCLUSION:

The results showed that myomectomy increased endometrial glycodelin (significantly) and GPx3 (not significantly) gene expression after 3 months. Study at different times and detecting expression of these genes can reveal more details.

 

 

Br J Cancer. 2014 Apr 2;110(7):1878-90.

Risk and prognosis of ovarian cancer in women with endometriosis: a meta-analysis.

Kim HS1Kim TH1Chung HH1Song YS2.

Abstract

BACKGROUND:

The risk and prognosis of ovarian cancer have not been well established in women with endometriosis. Thus, we investigated the impact of endometriosis on the risk and prognosis for ovarian cancer, and evaluated clinicopathologic characteristics of endometriosis-associated ovarian cancer (EAOC) in comparison with non-EAOC.

METHODS:

After we searched an electronic search to identify relevant studies published online between January 1990 and December 2012, we found 20 case-control and 15 cohort studies including 444,255 patients from 1,625 potentially relevant studies. In the meta-analysis, ovarian cancer risk by endometriosis and clinicopathologic characteristics were evaluated using risk ratio (RR) or standard incidence ratio (SIR), and prognosis was investigated using hazard ratio (HR) with 95% confidence interval (CI). Heterogeneity was evaluated using Higgins I(2) to select fixed-effect (I(2) ≤50%) or random effects models (I(2)>50%), and found no publication bias using funnel plots with Egger’s test (P>0.05). Furthermore, we performed subgroup analyses based on study design, assessment of endometriosis, histology, disease status, quality of study and adjustment for potential confounding factors to minimise bias.

RESULTS:

Endometriosis increased ovarian cancer risk in case-control or two-arm cohort studies (RR, 1.265; 95% CI, 1.214-1.318) and single-arm cohort studies (SIR, 1.797; 95% CI, 1.276-2.531), which were similar in subgroup analyses. Although progression-free survival was not different between EAOC and non-EAOC (HR, 1.023; 95% CI, 0.712-1.470), EAOC was associated with better overall survival than non-EAOC in crude analyses (HR, 0.778; 95% CI, 0.655-0.925). However, progression-free survival and overall survival were not different between the two groups in subgroup analyses. Stage I-II disease, grade 1 disease and nulliparity were more common in EAOC (RRs, 1.959, 1.319 and 1.327; 95% CIs, 1.367-2.807, 1.149-1.514 and 1.245-1.415), whereas probability of optimal debulking surgery was not different between the two groups (RR, 1.403; 95% CI, 0.915-2.152). Furthermore, endometrioid and clear cell carcinomas were more common in EAOC (RRs, 1.759 and 2.606; 95% CIs, 1.551-1.995 and 2.225-3.053), whereas serous carcinoma was less frequent in EAOC than in non-EAOC (RR, 0.733; 95% CI, 0.617-0.871), and there was no difference in the risk of mucinous carcinoma between the two groups (RR, 0.805; 95% CI, 0.584-1.109). These clinicopathologic characteristics were also similar in subgroup analyses.

CONCLUSIONS:

Endometriosis is strongly associated with the increased risk of ovarian cancer, and EAOC shows favourable characteristics including early-stage disease, low-grade disease and a specific histology such as endometrioid or clear cell carcinoma. However, endometriosis may not affect disease progression after the onset of ovarian cancer.

 

 

J Obstet Gynaecol Can. 2014 Feb;36(2):141-145.

Combined transurethral and laparoscopic partial cystectomy and robotically assisted bladder repair for the treatment of bladder endocervicosis: case report and review of the literature.

Rajakumar C1Vilos GA1Vilos AG1Marks JL1Ettler HC2Pautler SS3.

Abstract

BACKGROUND:

Endocervicosis, endosalpingiosis, endometriosis, and adenomyosis represent choristomas of Mullerian origin and are referred to as mullerianosis. These conditions frequently coexist, and they may present with pelvic pain, mass lesions, and/or infertility. Clinically, they are indistinguishable from one another, and histologically their epithelium is that of the endocervix, endosalpinx, or endometrium. Endocervicosis can be found in the urinary tract, frequently presenting as a bladder lesion or bladder dysfunction.

CASE:

We report here a case of bladder endocervicosis in a woman with extensive endometriosis and a bladder tumour who presented with chronic pelvic pain and infertility. Pelvic endometriosis was excised and vaporized with the CO2 laser, and the bladder lesion was excised in a combined transurethral and laparoscopic approach using the CO2 laser and robotic monopolar electrosurgical scissors. The cystotomy was then repaired using the robot, and the patient had an uneventful recovery with good clinical outcomes including spontaneous conception.

CONCLUSION:

Endocervicosis of the urinary bladder is a rare Mullerian choristoma. Symptomatic lesions can be removed surgically by various surgical techniques, and a collaborative team-based approach is in the patient’s best interest.

 

 

J Biophotonics. 2015 Jan;8(1-2):94-101

In vivo study of endometriosis in mice by photoacoustic microscopy.

Ding Y1Zhang MLang JLeng JRen QYang JLi C.

 

Abstract

Endometriosis (EM) impacts the healthcare and the quality of life for women of reproductive age. However, there is no reliable noninvasive diagnosis method for either animal study or clinical use. In this work, a novel imaging method, photoacoustic microscopy (PAM) was employed to study the EM on the mouse model. Our results demonstrated the PAM noninvasively provided the high contrast and 3D imaging of subcutaneously implanted EM tissue in the nude mouse in vivo. The statistical study also indicated PAM had high sensitivity and specificity in the diagnosis of EM in this animal study. In addition, we also discussed the potential clinical application for PAM in the diagnosis of EM.

 

 

 

Reprod Sci. 2014 Oct;21(10):1249-55.

FOXL2 in human endometrium: hyperexpressed in endometriosis.

Governini L1Carrarelli P1Rocha AL2Leo VD1Luddi A1Arcuri F1Piomboni P1Chapron C3Bilezikjian LM4Petraglia F5.

 

Abstract

The present study investigated expression and protein localization of FOXL2 messenger RNA (mRNA) in endometrium of healthy women and in patients with endometriosis during endometrial cycle. In endometriotic lesions, FOXL2 mRNA and protein were evaluated and a possible correlation with activin A mRNA expression changes was also studied. Endometrium was collected from healthy women (n = 52) and from women with endometriosis (n = 31) by hysteroscopy; endometriotic tissues were collected by laparoscopy (n = 38). FOXL2 gene expression analysis in endometrium of healthy women showed a significant expression and no significant changes in mRNA levels between proliferative and secretory phases; a similar pattern was observed in endometrium of patients with endometriosis. Immunohistochemical evaluation showed that FOXL2 protein localized in stromal and glandular cells and colocalized with SUMO-1. FOXL2 mRNA expression was 3-fold higher in endometriosis than in healthy endometrium (P < .01) and a positive correlation between FOXL2 and activin A mRNA was found (P < .05) in endometriosis. In conclusion, FOXL2 mRNA expression and its protein localization do not change during endometrial cycle in eutopic endometrium from healthy individuals or patients with endometriosis; the hyperexpression of FOXL2 in endometriotic lesions suggests an involvement of this transcriptional regulator, probably associated with activin A expression and related to the pathogenesis of endometriosis.

 

 

 

 

Exp Ther Med. 2014 Mar;7(3):685-690.

Shikonin reduces endometriosis by inhibiting RANTES secretion and mononuclear macrophage chemotaxis.

Yuan DP1Gu L2Long J3Chen J2Ni J2Qian N2Shi YL2.

 

Abstract

Endometriosis is a common disease in females of reproductive age and has the classic characteristic of mononuclear cell infiltration into lesions. Shikonin is an anti-inflammatory phytocompound obtained from Lithospermum erythrorhizon whose potential therapeutic effects in the treatment of endometriosis remain unclear. The working hypothesis of the present study was that shikonin is capable of inhibiting the development of endometriosis by inhibiting the chemotactic effect. In a murine model of endometriosis, shikonin significantly inhibited the growth of human endometrial tissue implanted into severe combined immunodeficiency (SCID) mice (P<0.05) and no adverse effects were observed. Mouse regulated upon activation normal T-cell expressed and secreted (mRANTES) levels in the peritoneal fluid of the animal endometriosis model were higher than those in normal SCID mice (P<0.05) and decreased significantly following shikonin treatment in a dose-dependent manner (P<0.05). Peritoneal fluid from SCID mice treated with shikonin inhibited the chemotaxis of monocytes; this inhibitory effect was eradicated by mRANTES antibody. In vitro, shikonin significantly inhibited RANTES expression in U937 cells that were cultured alone or co-cultured with human mesothelial and endometrial stromal cells. In addition, shikonin inhibited the RANTES-induced chemotaxis of U937 cells (P<0.05). The results indicate that shikonin inhibits the development of endometriosis by various mechanisms, including the inhibition of RANTES expression and the reduction of mononuclear cell migration to lesions. Therefore, shikonin may be a novel, useful and safe agent for treating endometriosis.

 

 

Int J Fertil Steril. 2013 Apr;7(1):33-8.

Comparison of expression of growth hormone-releasing hormone and its receptor splice variant 1 in different stages of endometriosis.

Wang Q1Wang Y2Fu X1Huang Y1.

Abstract

BACKGROUND:

The present study aims to explore the significance of the expression of growth hormone-releasing hormone (GHRH) and its receptor splice variant 1 (GHRHSV1) in endometriosis (EM).

MATERIALS AND METHODS:

In this research paper 80 EM patients who received treatment between March 2009 and September 2010 were selected, among which 20 were in stages I, II, III and IV respectively. 50 non-EM patients who underwent hysterectomy because of myoma during the same period comprised the control group. GHRH, GHRH-SV1 and their corresponding mRNA expression in eutopic endometrium and endometriotic tissue as well as ectopic endometrium were detected using immunohistochemical streptavidin-peroxidase (SP) and RT-PCR methods. Analysis of Variance (ANOVA) with Tukey Post Hoc test was used for data analysis and p<0.05 was considered significant.

RESULTS:

GHRH, GHRH-SV1 and their corresponding mRNA were expressed in eutopic endometrium and endometriotic tissue as well as ectopic endometrium. The mean optical density (OD) values of the GHRH and GHRH-SV1 expression in the experimental group were significantly higher than those in the normal group (p<0.05), and the relative intensity (RI) of GHRH mRNA and GHRH-SV1 mRNA expression in the experimental group was also significantly higher (p<0.05). The mean OD values of the GHRH and GHRHSV1 expression showed significant differences among endometriotic tissue at different stages of EM (p<0.05), and the RI of GHRH and GHRH-SV1 mRNA expression also showed significant differences (p<0.05).

CONCLUSION:

GHRH and GHRH-SV1 expression levels differ significantly at different stages of endometriosis.

 

 

Int J Fertil Steril. 2013 Apr;7(1):43-8.

Adiponectin effect on the viability of human endometrial stromal cells and mRNA expression of adiponectin receptors.

Bohlouli S1Khazaei M2Teshfam M1Hassanpour H3.

Abstract

BACKGROUND:

Adiponectin is one of the most important adipokines secreted from fatty tissue that has a direct inhibitory effect on the development of cancer cells. Adiponectin plays an important role in human reproduction system and fertility of women. Adiponectin concentration decreases in women with endometriosisand endometrial cancer. The aim of the present study was to investigate the effect of adiponectin on human endometrial stromal cell (HESC) viability as well as mRNA expression of Adipo R1 and Adipo R2 receptors.

MATERIALS AND METHODS:

In this experimental study, eight endometrial biopsies were taken and stromal cells were separated by enzymatic digestion and cell filtrations. Stromal cells of each biopsy were divided into four groups: control, 10, 100, and 200 ng/ml adiponectin concentrations. The effect of adiponectin on viability of the normal HESCs was studied by trypan blue staining and the relative expression levels of Adipo R1 and R2 were analyzed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Data were analyzed by one way ANOVA and unpaired student’s t test and p<0.05 was considered significant.

RESULTS:

Adiponectin decreased viability of normal human endometrial stromal cells in a dose and time dependent manner. Expression of Adipo R1 and Adipo R2 receptors did not change in the presence of adiponectin.

CONCLUSION:

Adiponectin can directly influence the viability of HESCs and decrease their viability, but it didn’t change expression of adiponectin receptors.

 

 

Int J Fertil Steril. 2013 Jul;7(2):96-9

Serum and peritoneal fluid levels of vascular endothelial growth factor in women with endometriosis.

Kianpour M1Nematbakhsh M2Ahmadi SM3Jafarzadeh M3Hajjarian M3Pezeshki Z2Safari T2Eshraghi-Jazi F2.

Abstract

BACKGROUND:

Endometriosis is known as one of the most common disease in women of reproductive age. Due to important role of vascular endothelial growth factor (VEGF) in neo-vascularization for the implantation of endometrial cell, and also presence of different studies reported VEGF level in the serum and peritoneal fluid (PF) in endometriosis patients, this study was designed to determine the serum and PF levels of VEGF in endometriosis patients, and to compare with normal subjects.

MATERIALS AND METHODS:

In this descriptive study, 179 women subjected to laparoscopy for the evaluation of infertility or pelvic pain were allocated into the following two groups: group I: different types of endometriosispatients (n=90) and group II: non-endometriosis patients (n=89). The PF from pelvis and venous blood samples were obtained. The VEGF concentration of the serum and PF were measured using enzyme immunoassay kit and were compared using t test.

RESULTS:

The level of VEGF in serum was significantly less than that in PF in both groups (p=0.00). However, endometriosis patients had significantly higher level of VEGF in peritoneal fluid than non-endometriosispatients (p=0.043).

CONCLUSION:

According to our findings, endometriosis is not associated with change in the level of circulating VEGF.

 

 

 

 

 

 

Int J Fertil Steril. 2013 Oct;7(3):207-16.

Pregnancy Rate after First Intra Cytoplasmic Sperm Injection- In Vitro Fertilisation Cycle in Patients with Endometrioma with or without Deep Infiltrating Endometriosis.

Oppenheimer A1Ballester M1Mathieu d’Argent E1Morcel K2Antoine JM1Daraï E1.

Abstract

BACKGROUND:

To evaluate the impact of the association of endometrioma with or without deep infiltrating endometriosis (DIE) after a first intra cytoplasmic sperm injection- in vitro fertilization (ICSI-IVF) cycle on pregnancy rate.

MATERIALS AND METHODS:

In this retrospective study, women with endometrioma who underwent a first ICSI-IVF cycle from January 2007 to June 2010 were reviewed for pregnancy rate. The main outcome measure was the clinical pregnancy rate. A multiple logistic regression (MLR) was performed; including all variables that were correlated to the conception rate. Only independent factors of pregnancy rate were included in a Recursive Partitioning (RP) model.

RESULTS:

The study population consisted of 104 patients (37 without DIE and 67 patients with associated DIE). Using multivariable analysis, a lower pregnancy rate was associated with the presence of DIE (OR=0.24 (95% CI: 0.085-0.7); p=0.009) and the use of ICSI (OR=0.23 (95% CI: 0.07-0.8); p=0.02). A higher pregnancy rate was associated with an anti-mullerian hormone (AMH) serum level over 1 ng/ml (OR=4.3 (95% CI: 1.1-19); p=0.049). A RP was built to predict pregnancy rate with good calibration [ROC AUC (95% CI) of 0.70 (0.65-0.75)].

CONCLUSION:

Our data support that DIE associated with endometrioma in infertile patients has a negative impact on pregnancy rate after first ICSI-IVF cycle. Furthermore, our predictive model gives couples better information about the likelihood of conceiving.

 

 

Neuro Endocrinol Lett. 2013;34(8):756-62

The role of vitamin D in impaired fertility treatment.

Grzechocinska B1Dabrowski FA1Cyganek A1Wielgos M1.

 

Abstract

Vitamin D is currently in the scope of research in many fields of medicine. Despite that its influence on health remains uncertain. This paper presents the review of the publications concerning the role of calciferol in reproduction processes and its significance in infertility therapy covering topics of polycystic ovary syndrome, endometriosis infertility, myoma infertility, male infertility, premature ovary failure and in vitro fertilization techniques. The results of latest research articles in those fields has been discussed and summarized. The deficiency of vitamin defined as the concentration of 25-hydroxycalciferol <20 ng/ml is frequently noted in patients of fertility clinics. Serum vitamin D concentration in healthy women is higher comparing to PCOS patients. The supplementation with vitamin D should be applied in the schemes of PCOS treatment both due to an improved insulin resistance and the results of infertility treatment. The explanation of vitamin D activity mechanism in patients with PCOS requires further research. Vitamin D have direct effect on AMH production, and thus increase longer maintenance of ovarian reserve in the patients with its higher concentration. The occurrence of uterine myomas in the group with vitamin D deficiency was evaluated as much higher comparing to controls. On the other hand it is supposed that high concentration of calciferol may be related to an impaired elimination of endometrial cells passing to peritoneal cavity via ovarian reflux causing endometriosis. In male infertility both low (<20 ng/ml) and high (>50 ng/ml) concentration of vitamin D in serum negatively affects spermatozoa number per ml of semen, their progressive movement and morphology. Significant differences as a response on ovulation stimulation, number and quality of embryos depending on vitamin D concentration were not observed in none of the analyzed papers concerning the role of vitamin D in in vitro fertilization (IVF). Better results in patients without calciferol insufficiency are explained by reports about high concentration of vitamin D and its metabolites in human in decidua collected in the 1st trimester of pregnancy which suggests its contribution in proper implantation and local immunological preference of the embryo. It is accepted that the treatment requires vitamin D concentration below 20 ng/ml (up to 50 nmol/l), especially in obese women, these with insulin resistance and small ovarian reserve and in men with oligo- and asthenozoospermia.

 

 

 

Am J Surg Pathol. 2014 Mar;38(3):305-15.

Primary endometrioid stromal sarcoma of the ovary: a clinicopathologic study of 27 cases with morphologic and behavioral features similar to those of uterine low-grade endometrial stromal sarcoma.

Oliva E1Egger JFYoung RH.

 

Abstract

Twenty-seven endometrioid stromal sarcomas of the ovary from patients 38 to 76 (mean 56) years of age are reported. The tumors were unilateral in 20 cases and bilateral in 7. They were solid (9), solid and cystic (9), or predominantly cystic (6) when this information was known and ranged from 1 to 20 (mean 9.5) cm. The solid areas typically had a tan-yellow cut surface, with areas of hemorrhage and/or necrosis noted in 6; however, in addition, blood was often present in the cyst lumens. On microscopic examination, the predominant and frequently exclusive pattern was a diffuse growth of small cells with interspersed arterioles, the latter appearing round to elongated. A fibromatous pattern was present in 14 of the tumors but was extensive in only 3. A vague nodular growth was observed in 10 tumors but was never striking; a storiform growth was seen in 2 tumors, being conspicuous in 1. Hyaline plaques were present in 10 tumors but were striking in only 2. Sex cord-like or smooth muscle differentiation was seen in 7 and 6 tumors, respectively, being striking in 2 and 3 of them. Foam cells were present in 6 tumors. The tumors showed minimal cytologic atypia. The mitotic index ranged from <1 to 17/10 high-power fields (HPF), being <1/10 HPF in 12, 1 to 5/10 HPF in 9, 6 to 10/10 HPF in 2, and >10/10 HPF in 4 tumors. Infarct-type necrosis was noted in 12 tumors. Hemorrhage, typically recent, was seen in 20 cases, being conspicuous in 5. Ovarian endometriosis was intimately associated with the tumor in 16 cases. Seven patients had stage I tumors, 5 stage II, 13 stage III, and 2 stage IV. Follow-up information was available for 21 patients; 10 were alive and free of disease from 4 to 21 years postoperatively (follow-up being ≥ 11 y in 5); 6 were alive with disease from 1 to 22 years postoperatively; 5 patients are known to have died of disease, with the interval being unknown in 1, and 2, 4, 13, and 17 years in the others. Follow-up information was unavailable in the remaining 6 patients. These findings indicate that these tumors, as in the uterus, often have an indolent course with a better prognosis than other ovarian sarcomas, indicating the importance of correct diagnosis. The differential diagnosis of these neoplasms is in the first instance with a metastasis from the uterus; knowledge of the status of the uterus is paramount in this distinction. Associated ovarian endometriosis suggests a primary tumor. When a primary ovarian origin is determined, the differential diagnosis is most often with a sex cord-stromal tumor, particularly a granulosa cell tumor because of a diffuse growth of cells with scant cytoplasm.

 

 

Surg Technol Int. 2014 Mar;24:243-8.

Disc resection is the first option in the management of rectal endometriosisfor unifocal lesions with less than 3 centimeters of longitudinal diameter.

de Almeida A1Fernandes LF2Averbach M2Abrão MS3.

 

Abstract

Rectosigmoid endometriosis is one of the most advanced forms of the disease affecting 3% to 37% of patients with endometriosis. Some patients are asymptomatic but others can develop severe symptoms such as abdominal and pelvic pain, diarrhea, constipation, and rectal bleeding. Transvaginal ultrasonography (USG-TV) with bowel preparation is the first-line investigation in patients with suspected bowel endometriosis and allows accurate determination of the presence of the disease. When endometriosis of rectosigmoid is diagnosed, the USG-TV helps the surgical team to define the appropriate therapeutic strategy, be it surgical or conservative. The surgical management of rectosigmoid endometriosis includes disc resection or segmental bowel resection. In recent years, disc resection has gained adherents; this approach allows the resection of macroscopic disease with fewer complications than segmental bowel resection. However, disc resection is only indicated when a lesion is unifocal, the size does not exceed 3 cm, and it does not involve more than 50% to 60% of circumference of the rectum or sigmoid wall. This article describes the laparoscopic disc resection surgical technique for intestinal deep endometriosis, its feasibility, and its current status.

 

 

Forensic Sci Int. 2014 Mar;236:22-9.

Non-traumatic and spontaneous hemothorax in the setting of forensic medical examination: a systematic literature survey.

Janik M1Straka L2Krajcovic J2Hejna P3Hamzik J4Novomesky F2.

 

Abstract

Spontaneous hemothorax is a well-known yet seldom-reported entity in forensic literature. While trauma-related hemothorax is frequently encountered in a medicolegal setting, non-traumatic and spontaneous hemothorax are relatively uncommon entities. The wide range of causes that can trigger fatal intrathoracic bleeding include thoracic aortic dissection, followed by vascular malformations, various oncological diseases, and connective tissue abnormalities. In rare instances, extramedullary hematopoiesis, ectopic pregnancy, congenital heart defects, amyloidosis, or parasitic diseases may constitute a source of bleeding. This etiological heterogeneity may, as a result, cause diagnostic difficulties during post-mortem elucidation of hemothorax. It should be borne in mind that hemothorax after low-energy trauma does not exclusively indicate traumatic hemorrhage, hence, the non-traumatic origin of bleeding must be taken into consideration. In this paper, we present a systematic review of the relevant literature enriched by the results of our observations to investigate the etiologies and recommendations for the post-mortem diagnosis of spontaneous hemothorax in an attempt to better delineate the possible medicolegal considerations. It is important that forensic pathologist as well as clinicians are aware of the diseases that could potentially give rise to fatal hemothorax.

 

 

J Minim Invasive Gynecol. 2014 Jul-Aug;21(4):682-8.

Long-term outcomes on quality of life in women submitted to laparoscopic treatment for bowel endometriosis.

Silveira da Cunha Araújo R1Abdalla Ayroza Ribeiro HS2Sekula VG2da Costa Porto BT2Ayroza Galvão Ribeiro PA2.

Abstract

STUDY OBJECTIVE:

To evaluate the long-term effects of laparoscopic surgery on quality of life in women with bowel endometriosis.

DESIGN:

Observational prospective cohort study (Canadian Task Force classification II).

SETTING:

Central Hospital of Santa Casa, Sao Paulo, Brazil.

PATIENTS:

Forty-five patients answered a short-form, 36-item, quality-of-life questionnaire (SF-36) at 3 different times.

INTERVENTIONS:

Between June 2007 and September 2008, patients underwent laparoscopic surgery to treat deep infiltrative endometriosis, with colorectal resection.

MEASUREMENTS AND MAIN RESULTS:

Forty-five patients with bowel endometriosis were followed up from 2007 to 2012. Before surgery, all patients exhibited signs suggestive of bowel endometriosis at magnetic resonance imaging and transrectal ultrasound. The patients underwent laparoscopic surgery for resection of the endometriosis lesions, including colorectal resection. The patients completed the questionnaire before surgery (T0), at 12 (T12) and 48 (T48) months after surgery. The 8 items of the SF-36 questionnaire at the different time points of application were compared. For each domain attribute, a score of 0 to 100 was assigned, where 0 signified the worst quality of life, and 100 the best. Statistical analysis was performed using analysis of variance. If differences were detected, multiple comparisons were performed using the Tukey test. Analysis of each domain revealed improved quality of life when comparing the period before surgery with 12 and 48 months after surgery. There was a significant increase (p < .001) in the scores in all of the SF-36 domains when comparing T0 vs T12 and T0 vs T48, with higher average scores at T48 corresponding to the domains of physical functioning, role physical, and social functioning (scores of 85.56, 75.69, and 73.61, respectively).

CONCLUSION:

Laparoscopic treatment of bowel endometriosis improved the long-term quality of life of patients.

 

 

Eur Spine J. 2014 May;23 Suppl 2:214-7.

Low back pain tied to spinal endometriosis.

Dongxu Z1Fei YXing XBo-Yin ZQingsan Z.

Abstract

STUDY DESIGN:

Case report.

OBJECTIVE:

We present a case of endometriosis of lumbar vertebrae. The literatures are reviewed with endometriosis of spine. Endometriosis is a common condition, which is defined as endometrial tissue lying outside the endometrial cavity. It is usually found within the peritoneal cavity, predominantly within the pelvis, commonly on the uterosacral ligaments. It can also be found in other sites such as umbilicus, abdominal scars, nasal passages and pleural cavity. But it is very rarely seen in the spine, with no report of endometriosis found in the lumbar vertebrae.

METHOD:

A 33-year-old woman presented with severe low back pain. She had the low back pain periodically for 3 years, and the pain was associated with menstruation. Radiographs showed a lesion in the posterior L3 body. After surgery, tissue biopsy indicated the presence of endometrial tissue in the lesion and thus confirmed endometriosis.

RESULTS:

Most cases of spine endometriosis that have been reported are usually found inside spinal canal, endorachis or spinal cord. But spinal vertebrae can also be involved in endometriosis.

CONCLUSIONS:

Although endometriosis is a rare possible cause of periodical low back pain in women of childbearing age, we suggest that if a woman suffering from periodical low back pain is encountered, do not ignore the possibility of endometriosis in the spine.

 

Reprod Sci. 2014 Aug;21(8):1027-1033.

Preoperative and Postoperative Clinical and Transvaginal Ultrasound Findings of Adenomyosis in Patients With Deep Infiltrating Endometriosis.

Lazzeri L1Di Giovanni A2Exacoustos C3Tosti C4Pinzauti S4Malzoni M2Petraglia F4Zupi E4.

Abstract

OBJECTIVES:

Deep infiltrating endometriosis (DIE) represents the most complex form of endometriosis and its treatment is still challenging. The coexistence of DIE with other appearances of endometriosis stimulates new studies to improve the preoperative diagnosis. Adenomyosis is a clinical form that shares several symptoms with DIE. The present study investigated the possible presence of adenomyosis in a group of women with DIE and its impact on pre- and postoperative symptoms.

MATERIALS AND METHODS:

A group of women (n = 121) undergoing laparoscopic treatment for DIE were enrolled. Clinical and ultrasound evaluations were performed as preoperative assessment. The ultrasonographical appearances of DIE and of adenomyosis were recorded by 2-dimensional ultrasound. The following symptoms were considered: dysmenorrhea, dyspareunia, abnormal uterine bleeding, bowel, and urinary symptoms. Pain was evaluated by the visual analog scale system and menstrual bleeding was assessed by the use of the pictorial blood assessment chart. In a subgroup of women (n = 55), a follow-up evaluation (3-6 months after surgery) was done.

RESULTS:

A relevant number of patients with DIE showed adenomyosis (n = 59; 48.7%); in this group, dysmenorrhea (P = .0019), dyspareunia (P = .0004), and abnormal uterine bleeding (P < .001) were statistically higher than that in the group with only DIE. After surgery, painful symptoms improved in the whole group but remained significantly higher (P < .001) in the group with adenomyosis.

CONCLUSIONS:

Deep infiltrating endometriosis is frequently associated with adenomyosis, significantly affecting pre- and postoperative symptoms and thus influencing the follow-up management.

 

 

 

Gynecol Endocrinol. 2014 May;30(5):381-4.

Serum YKL-40 levels are altered in endometriosis.

Tuten A1Kucur MImamoglu MOncul MAcikgoz ASSofiyeva NOzturk ZKaya BOral E.

 

Abstract

Endometriosis is traditionally defined as the presence of endometrial glands and stroma in ectopic locations, especially the pelvic peritoneum, ovaries and rectovaginal septum. YKL-40, a new biomarker of inflammation, is secreted by activated macrophages and neutrophils in different tissues with inflammation. Serum concentrations of YKL-40 are elevated in patients with diseases characterized by inflammation. We aimed to investigate the possible association between serum YKL-40 levels and endometriosis. A total number of 88 women were recruited for this case-control study. About 53 patients with surgically proven endometriosis were included, while 35 patients without endometriosis comprised the control group. Patients were classified as having minimal, mild, moderate and severe disease in accordance with the severity. Two new groups were formed by combining patients with minimal and mild disease (Stage 1-2) and with moderate and severe disease (Stage 3-4). Serum YKL-40 levels were statistically higher in the endometriotic group compared to control group (p:0.001). YKL-40 levels were significantly higher in Stage 3-4 group compared to Stage 1-2 group (p values 0.001) as well. Correlation analysis revealed a positive correlation between serum YKL-40 levels and the stage of the disease. YKL-40 may be utilized as a marker for determining the severity of endometriosis.

 

 

J Reprod Immunol. 2014 Jun;103:45-52.

Role of the CXCL12-CXCR4 axis in the development of deep rectal endometriosis.

Leconte M1Chouzenoux S2Nicco C2Chéreau C2Arkwright S3Santulli P4Weill B2Chapron C5Dousset B6Batteux F7.

 

Abstract

Immunological and angiogenetic factors enhance the implantation of endometrial cells in the peritoneal cavity. The aim of this work was to determine the role of the CXCL12-CXCR4 axis in the attraction and the peritoneal implantation of endometriotic stromal cells in deep infiltrating endometriosis (DIE). Biopsies of DIE nodules were obtained from 14 patients undergoing surgical treatment for DIE with low rectal involvement and from 12 patients without macroscopic endometriosis undergoing laparoscopy. CXCR4 expression was evaluated by Western blot analysis and flow cytometry in eutopic endometrial cells and DIE stromal cells in primary cultures derived from the biopsies. CXCL12-induced migration of DIE eutopic endometrial stromal cells was evaluated by transwell migration. CXCL12 was assayed in peritoneal fluids by ELISA. CXCR4 expression was higher in eutopic endometrial stromal cells than in control endometrial cells (p<0.05) and in DIE stromal cells (p<0.05). Eutopic endometrial stromal cells were more attracted by CXCL12 than control cells (p<0.01). CXCL12 was higher in DIE peritoneal fluids than in controls (p<0.05). CXCR4 was down-regulated in deep infiltrating endometriotic stromal cells. The CXCL12-CXCR4 axis plays a role in the attraction of eutopic endometrial cells into the peritoneal cavity, and the down-regulation of CXCR4 in resident endometriotic cells could cause their arrest in situ.

 

 

Int J Oncol. 2014 Apr;44(4):1394-400.

Plasminogen activators are involved in angiostatin generation in vivo in benign and malignant ovarian tumor cyst fluids.

van Tilborg AA1Sweep FC2Geurts-Moespot AJ2Wetzels AM1de Waal RM1Westphal JR1Massuger LF1.

 

Abstract

In many tumor types, angiogenesis is the net result of pro- and anti-angiogenic mediators and correlated with metabolic activity, growth, and degree of malignancy. One of the first discovered anti-angiogenic compounds is angiostatin, a proteolytic fragment of plasminogen. The requirements for in vivo angiostatin generation have not yet been determined. We investigated the levels of plasminogen and angiostatin by western blotting and of components of the plasminogen activator complex by ELISA in cyst fluid derived from benign and malignant ovarian tumors. Fluid samples from functional ovarian follicles, dermoid cysts and endometriotic lesions were evaluated separately. When no or minimal amounts of plasminogen were present in the cyst fluids, angiostatin was generally absent as well, irrespective of plasminogen activator concentrations. When plasminogen was present, the degree of conversion of plasminogen to angiostatin was significantly correlated with the level of uPA, and, to a lesser extent, to the tPA level. However, angiostatin was also found in a number of cyst fluid samples with minimal or no plasminogen activators, suggesting the involvement of other angiostatin generating proteases in these samples. Conversely, no angiostatin was observed in a number of cyst fluid samples containing both plasminogen and plasminogen activators. The presence of an inhibitor of the enzymatic activity of uPA and/or tPA, like PAI-1, may explain this finding. Our data show that plasminogen activators are clearly involved in in vivo angiostatin formation in ovarian cysts. Most likely, however, other proteases, as well as inhibitors of plasminogen activators, are involved as well.

 

 

Int J Clin Exp Pathol. 2014 Jan 15;7(2):648-55.

Dysregulated cell mechanical properties of endometrial stromal cells from endometriosis patients.

Wu ZY1Yang XM2Cheng MJ3Zhang R4Ye J5Yi H5Ao JP2Zhang ZG2Xu CJ6.

 

Abstract

Endometriosis, diagnosed with ectopically implanted endometrial stromal cells (ESC) and epithelial cells to a location outside the uterine cavity, seriously threaten the quality of life and reproductive ability of women, yet the mechanisms and the pathophysiology of the disease remain unclear. Specially, the functional changes of ESC during endometriosis progression need in-depth investigation. In this study, we characterized mechanical properties of normal ESC (NESC) from healthy women and eutopic ESC (EuESC) and ectopic ESC (EcESC) from endometriosis patients. We found the collagen lattice contractile ability of EuESC was significantly stronger than that of NESC, and the cell mobility of EuESC and EcESC was significantly greater than that of NESC. Furthermore, the expression of F-actin and vinculin in NESC, EuESC and EcESC cells progressively increased, and the Rho GTPase activity, of which RhoA exhibited the highest activity, in the three cells gradually increased. Collectively, these results suggest that the mechanical characteristics of NESC, EuESC and EcESC cells exhibited progressive abnormalities. Therefore, the biomechanics of endometrial stromal cells may be a potent target for intervention in patients with endometriosis.

 

 

Hum Reprod. 2014 May;29(5):946-52.

Adoptive transfer of pregnancy-induced CD4+CD25+ regulatory T cells reverses the increase in abortion rate caused by interleukin 17 in the CBA/JxBALB/c mouse model.

Wang WJ1Liu FJXin-LiuHao CFBao HCQu QLLiu XM.

Abstract

STUDY QUESTION:

Could adoptive transfer of pregnancy-induced CD4+CD25+ regulatory T cells (Tregs) reverse the increase in abortion rate caused by interleukin 17 (IL-17) in the CBA/J × BALB/c mouse model?

SUMMARY ANSWER:

The effects of exogenous IL-17 on increased abortion rate, as well as decreased transforming growth factor (TGF)-β and IL-10 expression, are reversed by a pre-mating transfusion of Tregs in a mouse model of pregnancy.

WHAT IS KNOWN ALREADY:

IL-17 is a pro-inflammatory cytokine mainly expressed by T helper 17 cells, and plays a pivotal role in the pathogenesis of endometriosis, miscarriage, preterm labor and pre-eclampsia. The activity of Th17 cells is attenuated by the anti-inflammatory action of Tregs.

STUDY DESIGN, SIZE, DURATION:

Fifty microliters of phosphate-buffered saline (PBS) (Group 1,) or recombinant IL-17 (rIL) (10 µg/mouse) supernatant (Group 2) was administered in the vaginal vaults of anesthetized pregnant CBA/J mice on Day 1 of pregnancy. Tregs (2 × 10(5) cells) purified from pregnant CBA/J × BALB/c mice were given i.v. via the tail vein 2 days before mating (Group 3) or on Day 7 of pregnancy (Group 4).

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Mice (n = 40) were randomly assigned to one of four experimental groups. The numbers of surviving and reabsorbed fetuses in each group were counted on Day 14 of pregnancy, and the expression of interferon (IFN)-γ, IL-4, TGF-β and IL-10 in the decidual tissue was assessed by real-time RT-PCR and western blotting.

MAIN RESULTS AND THE ROLE OF CHANCE:

Normal pregnant CBA/J mice mated with BALB/c males which received transvaginal rIL-17 presented with a significantly increased abortion rate compared with the group which received PBS (27.7 versus 9.9%, respectively; P < 0.05). The transfusion of pregnancy-induced Tregs from 14-day normal pregnant mice 2 days before mating reduced the abortion rate caused by IL-17 (12.5 versus 27.7%, respectively; P < 0.05), while transfusion of Tregs on Day 7 of pregnancy had no effect. Transfusion of Tregs did not affect IFN-γ or IL-4 expression in the decidual tissue at either the mRNA or protein level. Administration of rIL-17 resulted in a decrease in production of TGF-β and IL-10 at both mRNA and protein levels (P < 0.05). Transfusion of Tregs before mating increased TGF-β and IL-10 mRNA and protein levels (P < 0.05), while Tregs transfusion at Day 7 of pregnancy had no effect on TGF-β or IL-10 expression.

LIMITATIONS, REASONS FOR CAUTION:

These data derive from only a small number of mice. It is unclear whether the same effects would be seen in humans.

WIDER IMPLICATIONS OF THE FINDINGS:

Abnormally elevated expression of IL-17 in the feto-maternal interface may result in miscarriage. Transfer of antigen-specific Tregs before mating takes place may have potential applications in the prevention of recurrent spontaneous abortion.

STUDY FUNDING/COMPETING INTEREST(S):

This work was supported by a grant from the National Natural Science Foundation of China (81370013, 81000277 and 81300533) and Shandong Provincial Natural Science Foundation, China (ZR2013HQ002). There were no conflicts of interest.

Int J Gynecol Cancer. 2014 Mar;24(3):468-77.

Epithelial ovarian cancer: rationale for changing the one-fits-all standard treatment regimen to subtype-specific treatment.

Despierre E1Yesilyurt BTLambrechts SJohnson NVerheijen Rvan der Burg MCasado ARustin GBerns ELeunen KAmant FMoerman PLambrechts DVergote IEORTC GCG and EORTC GCG Translational Research Group.

Abstract

OBJECTIVE:

Epithelial ovarian cancers (EOCs) are, although still treated as a single disease entity, often classified into type I tumors (low-grade serous, mucinous, endometrioid, clear cell) and type II tumors (high-grade serous, undifferentiated cancers, carcinosarcomas). The aim of our study was to determine the incidence, clinical relevance, and prognostic and predictive impact of somatic mutations in both types I and II EOCs.

METHODS:

Two hundred sixty-two evaluable, primary, high-risk stage I (grade 3, or aneuploid grade 1 or 2, or clear cell) and stage II-IV EOCs, collected at the University Hospitals Leuven and within the European Organisation for Research and Treatment of Cancer 55971 trial, were genotyped for hotspot mutations in KRAS (COSMIC [Catalogue of Somatic Mutations in Cancer] coverage >97%), BRAF (>94%), NRAS (>97%), PIK3CA (>79%), PTEN, FBXW7 (>57%), AKT2, AKT3, and FOXL2, using Sequenom MassARRAY.

RESULTS:

Of the 13% histopathologically classified type I tumors, 49% were KRAS or PIK3CA mutant versus only 2.9% in the type II tumors (87%). Mucinous subtypes harbored significantly more KRAS mutations than all nonmucinous tumors (50% vs 4%, P < 0.001). PIK3CA mutations were predominantly found in clear cell carcinomas (46.2%) and endometrioid carcinoma (20%) and were frequently associated with endometriosis. Moreover, low-grade serous tumors were more frequently KRAS or BRAF mutated (44%) than high-grade serous tumors (0.6%). KRAS or PIK3CA mutation did not correlate with progression-free survival or overall survival. Mutations in NRAS, PTEN, FBXW7, AKT2, AKT3, and FOXL2 were rare (<1%).

CONCLUSIONS:

Somatic mutations are rare in type II EOCs, whereas type I EOCs contain distinct diseases with different driver mutations. In general, these tumors respond worse to standard paclitaxel carboplatin therapy. Clinical trials with molecular targeted therapy in the different subtypes of type I tumors are urgently needed using this theragnostic information.

 

 

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