Reprod Sci. 2014 Oct;21(10):1237-43.

Altered genome-wide methylation in endometriosis.

Naqvi H1Ilagan Y1Krikun G1Taylor HS2.

 

Abstract

Endometriosis has been associated with aberrant methylation in the eutopic endometrium. Using a genome-wide methylation array, we identified differentially methylated genes in the endometrium from women with or without endometriosis. One hundred and twenty genes were significantly altered by >1.5-fold. In all, 59 genes were significantly hypermethylated and 61 genes were significantly hypomethylated. Changes in gene expression associated with the altered methylation status were validated using quantitative real-time polymerase chain reaction. A limited number of candidate genes are selectively methylated in the endometrium of women with endometriosis. Several genes not previously associated with endometriosis are aberrantly methylated and expressed. These include O-6-methylguanine-DNA methyltransferase, dual specificity phosphatase 22, cell division cycle associated 2, inhibitor of DNA binding 2, retinoblastoma binding protein 7, bone morphogenetic protein receptor, type 1B, tumor necrosis factor receptor 1B, zinc finger protein receptor 681, immunoglobulin superfamily, member 21, and tumor protein 73. Aberrant DNA methylation and gene expression of these genes may contribute to abnormal regulation of endometrial cell proliferation and function in women.

 

 

Obstet Gynecol. 2014 May;123(5):1104-5.

What is new in chronic pelvic pain?: best articles from the past year.

Learman LA1.

 

Abstract

This month, we focus on current research in chronic pelvic pain, a condition defined by location (pelvis, anterior abdominal wall at or below the umbilicus, lumbosacral back, or buttocks), duration (6 or more months), and severity (sufficient to cause functional disability or to seek medical care). Dr. Learman discusses four recent publications, and each is concluded with a “bottom line” that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts.

 

 

Expert Opin Pharmacother. 2014 Jul;15(10):1403-15

Selective progesterone receptor modulators: an update.

Benagiano G1Bastianelli CFarris MBrosens I.

Abstract

INTRODUCTION:

Several selective progesterone receptor modulators (SPRMs) show promise in several areas of medicine and this work has been summarized by us in 2008.

AREAS COVERED:

Since the publication of our reviews, several developments have taken place in the field of reproductive medicine. The first is emergency contraception (EC). Two SPRMs are clinically utilized today: mifepristone (MFP) and ulipristal acetate (UPA). MFP is available for EC in up to 120 h following unprotected intercourse. A dose of 10 mg is significantly more effective than levonorgestrel (LNG). In a metanalysis of the use of UPA versus LNG up to 72 h after unprotected intercourse, failure rates of 1.4 versus 2.2% were reported. The second is contraception. A daily dose of 2 mg MFP can block ovulation and several MFP regimens are being tested, including a vaginal ring releasing MFP. The third is the preoperative administration in women harboring leiomyomas, where clinical testing of several SPRM has shown that they can decrease uterine leiomyomas’ size and substantially reduce uterine bleeding. SPRM can induce unusual, specific endometrial appearances. Many believe that these changes should not cause concern, but the issue remains controversial.

 

 

Chin Med J (Engl). 2014;127(9):1761-7.

Tumor necrosis factor gene polymorphisms and endometriosis in Asians: a systematic review and meta-analysis.

Lyu J1Yang H1Lang J1Tan X2.

Abstract

BACKGROUND:

Numerous studies have described the association between polymorphisms in the tumor necrosis factor (TNF) gene and risk of endometriosis. However, the results remain controversial. Here we reviewed studies reporting the association between TNF gene polymorphisms and endometriosis risk in Asians.

METHODS:

PubMed and Embase were searched. Twelve case-control studies assessing the role of multiple TNF gene polymorphisms in endometriosis were included. If no less than two articles evaluated one variant, meta-analysis was conducted; otherwise, narrative analysis was chosen. A fixed- or random-effects model was employed according to the heterogeneity among studies. The strength of the association between TNF gene polymorphisms and endometriosis risk was assessed by odds ratios and 95% confidence intervals.

RESULTS:

For TNF-α -238G>A, -308G>A, -857C>T, and -863C>A, no significant associations were identified from all genetic models. For TNF-a -850T>C, results from one study showed that patients harboring the heterozygote TC were less susceptible to endometriosis than patients harboring the homozygote TT. For TNF-a -1031T>C, a mild increase in endometriosis risk was found in the Asian population. Meta-analysis from two studies found that the TNF-β +252>G polymorphism had a protective effect in Chinese individuals. Due to the limitations of the included studies, it is necessitated to perform more studies to elucidate the possible roles of TNF gene polymorphisms in the pathogenesis of endometriosis.

CONCLUSIONS:

TNF-α -1031T>C and TNF-β +252A>G were significantly associated with the risk of endometriosis in Asian and Chinese populations, respectively. To further evaluate these associations, more large-scale, rigorously designed studies are needed.

 

 

Arch Gynecol Obstet. 2014 Nov;290(5):919-24.

Surgical outcome of deep infiltrating colorectal endometriosis in a multidisciplinary setting.

Bachmann R1Bachmann CLange JKrämer BBrucker SYWallwiener DKönigsrainer AZdichavsky M.

Abstract

BACKGROUND:

Endometriosis as a benign disease appears frequently in premenopausal women with highly variable symptoms. In advanced stages bowel involvement is common. In symptomatic disease the adequate treatment requires complete resection of all residues. Indications of colorectal resection for endometriosisremain controversial because of the risk of major complications. The purpose of this study was to show the feasibility of planned complete laparoscopic management of symptomatic deep pelvic endometriosis with bowel involvement performing segmental colorectal resection in a center of excellence.

METHODS:

Between 2007 and 2012 all patients treated for symptomatic colorectal endometriosis in our institution were included and retrospectively evaluated. Laparoscopic excision of all visible disease was planned. Data analysis included age, previous history of endometriosis, intraoperative findings, operative procedure and intra- and postoperative complications.

RESULTS:

In this time period 35 patients with bowel infiltrating endometriosis were treated. Affected locations were the rectovaginal space in 31 patients (89 %), the rectum in 32 patients (91 %), the sigmoid colon in 10 patients (29 %), the coecum in 2 patients (5.7 %), the appendix in 3 patients (8.6 %) and the terminal ileum in 1 patient (2.9 %). In the majority of patients (85.7 %) the resection was achieved laparoscopically, in 3 patients a conversion to laparotomy was necessary and in 2 patients a primary laparotomia was performed. Complications occurred in 2 cases with anastomotic leakage in 1 patient (2.8 %) and a rectovaginal fistula in another patient. Radical resection was achieved in almost all patients (97 %).

CONCLUSIONS:

A well-trained interdisciplinary team can perform treatment of deep infiltrating endometriosislaparoscopically with low incidence of major complications as anastomotic leakage or rectovaginal fistula. Criteria of complete endometriosis restoration of the rectum can be achieved by total or subtotal rectal excision.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Jul;178:89-94.

Isolation and identification of epithelial and stromal stem cells from eutopic endometrium of women with endometriosis.

Li T1He H1Liu R1Wang SX1Pu DM2.

Abstract

OBJECTIVE:

The recent characterization of possible stem/progenitor cells in the endometrium has shed new light on the origins of ectopic endometrial tissue and the mechanism for the pathogenesis of endometriosis, but has raised new questions. Is it possible that abnormal endometrial stem/progenitor cells increase their capacity to implant and establish themselves as ectopic tissue, or that normal stem cells implant in abnormal peritoneum? This study investigated key stem cell properties in cologenic epithelial and stromal cells obtained from eutopic endometrium of women with endometriosis.

STUDY DESIGN:

Single cell suspensions of endometrial epithelial and stromal cells were cultured at densities of 20, 50, 100 and 200cells/cm(2). Cloning efficiency (CE) was determined, and stem cell phenotypic surface markers were detected using Western blotting and quantitative real-time polymerase chain reaction.

RESULTS:

CE was significantly higher in cells cultured at a density of 50cells/cm(2) compared with the other groups. After 15 days of culture, small and large colonies were observed. Large-colony-derived epithelial and stromal cells had high proliferative potentials, producing millions of cells in vitro, with strong expression of epithelial and stromal stem cell phenotypic surface markers EMA, CK, CD49f, THY-1(CD90), collagen type I, 5B5 and vimentin.

CONCLUSION:

Adult stem cells were found in eutopic endometrium of women with endometriosis, and this may play an important role in disease development.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Jun;177:48-51.

Dienogest improves human leucocyte antigen-DR underexpression and reduces tumour necrosis factor-α production in peritoneal fluid cells from women with endometriosis.

Maeda N1Izumiya C2Taniguchi K2Matsushima S2Mita S3Shimizu Y3Fukaya T2.

Abstract

OBJECTIVE:

To determine the immunological effect of dienogest (DNG), an oral anti-endometriosis drug, on peritoneal fluid (PF) macrophages collected from women with endometriosis. Although it has been suggested that DNG has direct effects on endometriotic cells, including decreased cell proliferation and decreased anti-inflammatory cytokine production, the effects of DNG on PF cells are unclear.

STUDY DESIGN:

The effects of DNG on PF cells from 34 women with endometriosis and 22 women without endometriosis (controls) were investigated. Expression of human leucocyte antigen (HLA)-DR in PF macrophages, obtained from the peritoneal cavity during laparoscopic surgery, was determined by flow cytometry. HLA-DR expression was measured again after PF cells had been cultured for 72 h in a humidified atmosphere at 37 °C in 5% CO₂-95% air with or without DNG. After 72 h of incubation, the concentration of pro-inflammatory tumour necrosis factor (TNF)-α in the media was measured by enzyme-linked immunosorbent assay.

RESULTS:

HLA-DR expression was lower in PF macrophages from women with endometriosis compared with controls. However, after DNG treatment, HLA-DR expression in PF macrophages from women with endometriosis was increased to the same level as in controls. The TNF-α concentration in the media was decreased by DNG.

CONCLUSIONS:

DNG can restore the antigen-presenting ability of PF macrophages by increased HLA-DR expression, and may have an anti-inflammatory effect on PF macrophages in women with endometriosis.

 

 

Fertil Steril. 2014 Jul;102(1):143-150.

Ultrasound mapping system for the surgical management of deep infiltrating endometriosis.

Exacoustos C1Malzoni M2Di Giovanni A2Lazzeri L3Tosti C3Petraglia F3Zupi E3.

Abstract

OBJECTIVE:

To assess the accuracy of transvaginal sonography (TVS) in defining size and location of deep infiltrating endometriosis (DIE) with laparoscopic/histologic confirmation.

DESIGN:

Prospective observational study.

SETTING:

University hospital.

PATIENT(S):

One hundred four women with suspected DIE on the basis of TVS.

INTERVENTION(S):

Patients with DIE underwent TVS evaluation before laparoscopic surgery. An accurate mapping of the extent of the disease was recorded during TVS and at laparoscopy. This new mapping system was developed to assess the extent of endometriosis by measuring the size and depth of the lesions at the various pelvic locations.

MAIN OUTCOME MEASURE(S):

Surgical and histologic confirmation of the ultrasonographic data to evaluate the presence and location of DIE and creation of a new mapping methodology for detecting DIE by TVS.

RESULT(S):

Depending on the different location of the lesions, the accuracy of TVS ranged from 76%-97%. The lowest sensitivity (59%) and accuracy (76%) were obtained for TVS in the diagnosis of vaginal endometriosis, whereas the greatest accuracy (97%) was shown in detecting bladder lesions and Douglas obliteration.

CONCLUSION(S):

This new ultrasound mapping system is accurate for detecting the extent of DIE and may be useful for preoperative planning and intraoperative management of symptomatic patients with DIE.

 

 

Gynecol Surg. 2014;11:105-112.

A European survey on awareness of post-surgical adhesions among gynaecological surgeons.

Wallwiener M1Koninckx PR2Hackethal A3Brölmann H4Lundorff P5Mara M6Wattiez A7De Wilde RL8for The Anti-Adhesions in Gynecology Expert Panel (ANGEL).

 

Abstract

The present survey was conducted among gynaecological surgeons from several European countries to assess the actual knowledge and practice related to post-surgical adhesions and measures for reduction. From September 1, 2012 to February 6, 2013, gynaecological surgeons were invited to answer an 18-item online questionnaire accessible through the ESGE website. This questionnaire contained eight questions on care settings and surgical practice and ten questions on adhesion formation and adhesion reduction. Four hundred fourteen surgeons participated; 70.8 % agreed that adhesions are a source of major morbidity. About half of them declared that adhesions represented an important part of their daily medical and surgical work. About two thirds informed their patients about the risk of adhesion. Most cited causes of adhesions were abdominal infections and extensive tissue trauma, and endometriosis and myomectomy surgery. Fewer surgeons expected adhesion formation after laparoscopy (18.9 %) than after laparotomy (40.8 %); 60 % knew the surgical techniques recommended to reduce adhesions; only 44.3 % used adhesion-reduction agents on a regular basis. This survey gives a broad picture of adhesion awareness amongst European gynaecological surgeons, mainly from Germany and the UK. The participants had a good knowledge of factors causing adhesions. Knowledge of surgical techniques recommended and use of anti-adhesion agents developed to reduce adhesions need to be improved.

 

 

Zhongguo Zhen Jiu. 2014 Feb;34(2):139-44.

Efficacy observation on the combination of acupuncture and Chinese medication in prevention of the recurrence of endometriosis after laparoscopic surgery.

Zhang XYZhang CY.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of acupuncture-moxibustion combined with modified Mojie tablet (see text) in the prevention of the recurrence of endometriosis (EMS) after laparoscopic surgery.

METHODS:

After laparoscopic surgery, 120 cases of EMS were randomized into an acupuncture-moxibustion group, a western medication group, a Chinese medication group and a combined therapy of acupuncture-moxibustion and Chinese medication group (combined therapy group), 30 cases in each one. In the acupuncture-moxibustion group, acupuncture was applied at Xuehai (SP 10), Sanyinjiao (SP 6) and Guanyuan (CV 4); the isolated moxibustion with ginger was used at Guanyuan (CV 4), once a day, twice a week. In the western medication group, gestrinone was prescribed for oral administration, 2.5 mg, once a day, twice a week. In the Chinese medication group, the self-prepared Mojie tablet were prescribed for oral administration. In the combined therapy group, acupuncture, moxibustion and modified Mojie tablet for oral administration were used in combination. The therapeutic methods were same as the acupuncture-moxibustion group and the Chinese medication group. Totally, the treatment of 3 months was required. Separately, before treatment, after treatment, in 3 months after treatment and in 6 months after treatment, EHP-5 score (endometriosis health profile-5), the abdominal/vaginal ultrasound examination, serum CA125 detection and safety index (ALT detection) were compared in patients among 4 groups.

RESULTS:

In 3 and 6 months after treatment, the positive rates of EHP-5 score were 0% (0/30) in the combined therapy group and 0% (0/30) in the acupuncture-moxibuston group, which were all lower significantly than 13.3% (4/30) in the western medication group (both P < 0.05). In follow-up stage of 6 months after treatment, there was no recurrence case in abdominal lviginal ultrasound examination in the combined therapy group, which was lower than 13.3% (4/30) in the western medication group (P < 0.05); the serum CA125 detection in the combined therapy group did not find any abnormal case, which was lower than 16.7% (5/30) in the western medication group (P < 0.05). At the end of treatment session and in the follow-up stage of 3 months after treatment, the abnormal rate of ALT were 20.0% (6/30) and 13.3% (4/30) in the western medication group, which were higher than those in any of the rest groups (P < 0.05). In the follow-up stage of 6 months after treatment, there were 3 abnormal cases of ALT in the western medication group, but which was not different significantly as compared with the rest groups (P > 0.05).

CONCLUSION:

Acupuncture and moxibustion combined with modified Mojie tablet effectively prevent from the recurrence of EMS after laparoscopic surgery and improve the life quality of the patients. This combined therapy brings less damage on the liver as compared with the western medication of gestrinone and indicates its definite efficacy and safety.

 

 

 

Fertil Steril. 2014 Aug;102(2):496-502.

Common variants in the CYP2C19 gene are associated with susceptibility to endometriosis.

Painter JN1Nyholt DR2Krause L2Zhao ZZ2Chapman B2Zhang C3Medland S2Martin NG2Kennedy S4Treloar S5Zondervan K6Montgomery GW2.

Abstract

OBJECTIVE:

To follow-up previous studies highlighting a possible role for cytochrome P450, family 2, subfamily C, 19 (CYP2C19) in susceptibility to endometriosis by searching for additional variants in the CYP2C19 gene that may be associated with the disease.

DESIGN:

Case-control study.

SETTING:

Academic research.

SUBJECT(S):

The cases comprised 2,271 women with surgically confirmed endometriosis; the controls comprised 939 women with self-report of no endometriosis and 1,770 unscreened population samples.

INTERVENTION(S):

Sequencing of the CYP2C19 region and follow-up of 80 single nucleotide polymorphisms (SNPs) in two case-control samples.

MAIN OUTCOME MEASURE(S):

Allele frequency differences between cases and controls.

RESULT(S):

Sequencing of the CYP2C19 gene region resulted in the detection of a large number of known and novel SNPs. Genotyping of 80 polymorphic SNPs in 901 endometriosis cases and 939 controls resulted in study-wide significant association signals for SNPs in moderate or complete linkage disequilibrium with rs4244285, a functional SNP in exon 5 that abrogates CYP2C19 function through the creation of an alternative splice site. Evidence of association was also detected for another functional SNP in the CYP2C19 promoter, rs12248560, which was highlighted in our previous study.

CONCLUSION(S):

Functional variants in CYP2C19 may contribute to endometriosis susceptibility in both familial and sporadic cases.

 

 

J Clin Endocrinol Metab. 2014 Sep;99(9):3450-9

Transforming growth factor-β induced Warburg-like metabolic reprogramming may underpin the development of peritoneal endometriosis.

Young VJ1Brown JKMaybin JSaunders PTDuncan WCHorne AW.

Abstract

CONTEXT:

TGF-β is believed to play a major role in the etiology of peritoneal endometriosis. In tumors, TGF-β induces the metabolic conversion of glucose to lactate via glycolysis, a process referred to as the “Warburg effect.” Lactate increases cell invasion, angiogenesis, and immune suppression, all crucial steps in the development of endometriosis.

OBJECTIVE:

The aim of this study was to determine whether TGF-β induces a “Warburg-like” effect in peritoneal endometriosis.

DESIGN:

The study was informed by human tissue analysis and cel culture.

SETTING:

The study was conducted at the university research institute.

PATIENTS OR OTHER PARTICIPANTS:

We studied women undergoing surgical investigation for endometriosis.

INTERVENTIONS:

Concentrations of lactate and TGF-β1 in peritoneal fluid (n = 16) were measured by commercial assay. Expression of genes implicated in glycolysis was measured in endometrial and peritoneal biopsies (n = 31) by quantitative RT-PCR and immunohistochemistry. The effect of TGF-β1 on primary human peritoneal mesothelial cells (n = 6) and immortalized mesothelial (MeT-5A) cells (n = 3) was assessed by quantitative RT-PCR, Western blot, and commercial assays.

MAIN OUTCOME MEASURES:

Lactate, TGF-β1, and markers of glycolysis were measured.

RESULTS:

Concentrations of lactate in peritoneal fluid paralleled those of TGF-β1, being significantly higher in women with endometriosis compared to women without (P < .05). Endometriosis lesions expressed higher levels of glycolysis-associated genes HIF1A, PDK1, and LDHA than eutopic endometrium, and adjacent peritoneum had higher levels of HIF1A and SLC2A1 than peritoneum from women without disease (P < .05 to P < .001). Exposure of mesothelial cells to TGF-β1 increased production of lactate (P < .05), increased HIF1A mRNA (P < .05), and protein, and increased concentrations of mRNAs encoded by glycolysis-associated genes (LDHA, PDK1, SLC2A1; P < .05).

CONCLUSIONS:

A change in the metabolic phenotype of endometriosis lesions and peritoneal mesothelium in women with endometriosis may favor development of endometriosis.

 

 

Am J Obstet Gynecol. 2014 Oct;211(4):358.e1-6.

Premenstrual spotting of ≥2 days is strongly associated with histologically confirmed endometriosis in women with infertility.

Heitmann RJ1Langan KL1Huang RR2Chow GE1Burney RO3.

Abstract

OBJECTIVE:

The purpose of this study was to assess the prevalence of endometriosis in women with premenstrual spotting and to determine the predictive value of this symptom in the diagnosis of endometriosis.

STUDY DESIGN:

We conducted a retrospective cohort study of 80 consecutive women who presented to the infertility clinic for evaluation and who subsequently underwent laparoscopic assessment for infertility with or without pelvic pain. Our main outcome measure was the presence or absence of histologically confirmed endometriosis in women with and without premenstrual spotting.

RESULTS:

Endometriosis was significantly more prevalent in subfertile women who reported premenstrual spotting for ≥2 days relative to women without this symptom (89% [34/38 women] vs 26% [11/42 women]; P < .0001). Multinomial logistic regression analysis demonstrated the presence of premenstrual spotting for ≥2 days to be associated significantly with the presence of endometriosis (odds ratio, 16; 95% confidence interval, 3.9-65.4; P < .01) and red vesicular lesion type (odds ratio, 52.6; 95% confidence interval, 8.6-323.1; P < .001).

CONCLUSION:

In this cohort of women with infertility, premenstrual spotting of ≥2 days was associated strongly with histologically confirmed endometriosis and a better predictor than dysmenorrhea or dyspareunia of finding endometriosis at laparoscopy. Premenstrual spotting of at least 2 days was also associated strongly with both higher stage disease and the red vesicular peritoneal endometriosis phenotype.

 

 

Case Rep Obstet Gynecol. 2014;2014:421234.

Reactive nodular fibrous pseudotumor: case report and review of the literature.

Salihi R1Moerman P2Timmerman D1Van Schoubroeck D1Op de Beeck K3Vergote I1.

 

Abstract

We will describe a case of a patient diagnosed with a rare identity of a benign lesion, “reactive nodular fibrous pseudotumor” (RNFP). It is a tumor which preoperatively can present as a malignant tumor and is only reported in 19 cases. According to the very limited amount of information on this tumor in the literature it is mostly seen after trauma or intraperitoneal inflammation. Our case is the second one of RNFP associated with endometriosis, which is a frequently seen intraperitoneal inflammation process in women. Knowledge that these large pseudotumoral lesions can occur is important to direct the management of these patients.

 

 

 

 

 

J Expo Sci Environ Epidemiol. 2015 May;25(3):278-85.

Persistent organic pollutants (POPs) and fibroids: results from the ENDO study.

Trabert B1Chen Z2Kannan K3Peterson CM4Pollack AZ5Sun L2Buck Louis GM2.

 

Abstract

To evaluate the association between persistent organic pollutants (POPs) and uterine fibroids, we used previously collected data from a cohort of women aged 18-44 years undergoing laparoscopy or laparotomy at 14 participating hospital surgical centers (n=473). POP concentrations were measured in omental fat and serum. Presence of fibroids was defined on the basis of a postoperative diagnosis (n=99). Odds ratios (OR) and 95% confidence interval (CI) for each POP by biologic medium were estimated using unconditional logistic regression adjusted for identified covariates. Concentrations were higher in omental fat than in serum for all POPs. Serum p,p’-dichlorodiphenyldichloroethylene (p,p’-DDE) was the only POP associated with fibroids (per 1-SD increase in log-transformed p,p’-DDE OR (95% CI): 1.37 (1.05-1.80)). In analyses excluding women diagnosed with endometriosis, a number of polychlorinated biphenyls (PCBs) measured in omental fat were associated with fibroids (PCB 99: 1.64 (1.08, 2.49); PCB 138: 1.64 (1.03, 2.59); PCB 146: 1.54 (1.01, 2.37); PCB 153: 1.88 (1.12, 3.13); PCB 196: 1.60 (1.02, 2.51); PCB 206: 1.52 (1.01, 2.29)). Although exploratory, our study suggests that PCBs may be associated with fibroids in the absence of other gynecologic disorders such as endometriosis, but the associations varied by biologic media with more POPs emerging when quantified in fat.

 

 

Biomed Res Int. 2014;2014:236821.

Looking for celiac disease in Italian women with endometriosis: a case control study.

Santoro L1Campo S2D’Onofrio F3Gallo A3Covino M3Campo V2Palombini G4Santoliquido A3Gasbarrini G3Montalto M3.

 

Abstract

In the last years, a potential link between endometriosis and celiac disease has been hypothesized since these disorders share some similarities, specifically concerning a potential role of oxidative stress, inflammation, and immunological dysfunctions. We investigated the prevalence of celiac disease among Italian women with endometriosis with respect to general population. Consecutive women with a laparoscopic and histological confirmed diagnosis of endometriosis were enrolled; female nurses of our institution, without a known history of endometriosis, were enrolled as controls. IgA endomysial and tissue transglutaminase antibodies measurement and serum total IgA dosage were performed in both groups. An upper digestive endoscopy with an intestinal biopsy was performed in case of antibodies positivity. Presence of infertility, miscarriage, coexistence of other autoimmune diseases, and family history of autoimmune diseases was also investigated in all subjects. Celiac disease was diagnosed in 5 of 223 women with endometriosis and in 2 of 246 controls (2.2% versus 0.8%; P = 0.265). Patients with endometriosis showed a largely higher rate of infertility compared to control group (27.4% versus 2.4%; P < 0.001). Our results confirm that also in Italian population an increased prevalence of celiac disease among patients with endometriosis is found, although this trend does not reach the statistical significance.

 

Gynecol Endocrinol. 2014 Sep;30(9):644-8.

Dienogest reduces proliferation, aromatase expression and angiogenesis, and increases apoptosis in human endometriosis.

Miyashita M1Koga KTakamura MIzumi GNagai MHarada MHirata THirota YFujii TOsuga Y.

 

Abstract

Dienogest is a novel progestin that is highly selective for progesterone receptors and inhibits endometriosis. However, it remains unknown how the administration of dienogest to patients with endometriosis impacts on their lesion tissues. The aim of this study was to evaluate the in vivo effect of dienogest on endometriosis tissue. We collected endometrioma tissues from patients treated with dienogest (N = 7) or not treated (N = 11, controls). Cell proliferation, aromatase expression and blood vessel density were evaluated by staining for Ki67, aromatase and the von Willebrand factor, respectively. Apoptosis was detected using the TUNEL assay. The proportion of Ki67 and aromatase positive epithelial cells was significantly lower in the dienogest group than in controls (p < 0.05, respectively). The number of TUNEL positive cells was significantly higher in the dienogest group (p < 0.05). The density of blood vessels in endometrioma was marginally lower in the dienogest group compared with controls (p = 0.20). Our study demonstrates that endometrioma taken from patients treated with dienogest show remarkable histological features such as reduction of proliferation, aromatase expression and angiogenesis, and increase of apoptosis. This study clarified the impact of dienogest on local histological events that explain its therapeutic effect on endometriosis.

 

 

 

Am J Reprod Immunol. 2014 Sep;72(3):262-9.

Characterization of uterine NK cells in women with infertility or recurrent pregnancy loss and associated endometriosis.

Giuliani E1Parkin KLLessey BAYoung SLFazleabas AT.

Abstract

PROBLEM:

Uterine natural killer cells (uNK) have been thought to play a key role in endometriosis and infertility. We investigated the expression of CD56, CD16, and NKp46 in endometrial tissues from 61 women with unexplained recurrent pregnancy loss (uRPL) or infertility (UI) and correlated this with the presence or absence of endometriosis. The results from the patients with subfertility were compared with those from 10 fertile patients.

METHOD OF STUDY:

Mid-secretory phase endometrial biopsies were obtained, and the endometrial expression of CD56, CD16, or NKp46 was identified by immunohistochemistry and quantified (ImageJ Software).

RESULTS:

The percentage of CD16(+) cells was higher in women with uRPL (7.9 ± 3.2) and UI (9.0 ± 5.5), even when these conditions were associated with endometriosis (8.9 ± 5.3), compared with fertile patients (5.6 ± 2.4, P < 0.05). Likewise, the ratio of NKp46(+) :CD56(+) cells was higher in women with uRPL (0.28 ± 0.25) and UI (0.21 ± 0.2), even when these conditions were associated with endometriosis (0.19 ± 0.14), compared with fertile patients (0.1 ± 0.1, P < 0.05). No differences were observed when comparing CD56.

CONCLUSIONS:

Women, with or without endometriosis, who have larger populations of cytotoxic CD16(+) uNK cells and/or higher populations of NKp46(+) CD56(+) cells may be at greater risk of infertility disorders resulting from an inflammatory environment occurring during implantation or later during decidualization.

 

 

Reprod Sci. 2015 Jan;22(1):124-31.

The potential role of endometrial nerve fibers in the pathogenesis of pain during endometrial biopsy at office hysteroscopy.

Di Spiezio Sardo A1Florio P2Fernandez LM1Guerra G3Spinelli M1Di Carlo C1Filippeschi M4Nappi C1.

 

Abstract

We aimed to evaluate whether nerve fibers are present in the endometrial layer of patients submitted to office hysteroscopy and their potential contribution to the pathogenesis of pain during that procedure. Through a prospective case-control study performed in tertiary centers for women’s health, endometrium samples were collected during operative office hysteroscopy from 198 cycling women who previously underwent laparoscopy and/or magnetic resonance imaging investigation for infertility assessment. Samples were classified according to the degree of the pain patients experienced and scored from values ranging from 0 (absence of discomfort/pain) to 10 (intolerable pain) on a 10-cm visual analog scale (VAS). The presence of nerve fiber markers (S100, NSE, SP, VIP, NPY, NKA, NKB, NKR1, NKR2, and NKR3) in the endometrium was also evaluated by morphologic and immunohistochemical analyses. We found that S-100, NSE, NKR1, NK-A, NK-B, VIP, and NPY, were immunolocalized in samples of endometrium, in significantly (P < .01, for all) higher levels in samples collected from patients with VAS score > 5 (group A) than ≤ 5 (group B) and significantly (P < .0001 for all) positively correlated with VAS levels. A statistically significant (P = .018) higher prevalence of endometriosisand/or adenomyosis was depicted in patients of group A than group B. Data from the present study led us to conclude that nerve fibers are expressed at the level of the functional layer of the endometrium and may contribute to pain generation during office hysteroscopy, mainly in women affected by endometriosis and adenomyosis.

 

 

Int J Urol. 2014 Apr;21 Suppl 1:85-8.

Gynecological disorders in bladder pain syndrome/interstitial cystitis patients.

Cervigni M1Natale F.

Abstract

OBJECTIVES:

Bladder pain syndrome/interstitial cystitis, a chronic inflammatory condition of the bladder, is the source of pain in over 30% of female patients with chronic pelvic pain. The aim of the present study was to evaluate the most frequent associations between bladder pain syndrome/interstitial cystitis and gynecological disorders.

METHODS:

A literature review of the previous 10 years was carried out to evaluate the incidence of gynecological diseases in patients with bladder pain syndrome/interstitial cystitis.

RESULTS:

Hypertonic pelvic floor dysfunction with associated voiding dysfunction can be present in bladder pain syndrome/interstitial cystitis patients. It has been estimated that the prevalence ranges from 50% to 87%. Endometriosis affects 1-7% of the general population and up to 70% of women with endometriosis have some type of pain symptoms, a recent systematic review estimated the prevalence of bladder pain syndrome to be 61%, of endometriosis to be 70%, and coexisting bladder pain syndrome and endometriosis to be 48%. Vulvodynia is represented by pain, or an unpleasant altered sensation, in the vulva. Women with vestibulodynia are likely to have other additional pain conditions, such as fibromyalgia, irritable bowel syndrome or chronic fatigue syndrome. Recent data reported that vestibulodynia affects 25% of women with bladder pain syndrome/interstitial cystitis.

CONCLUSIONS:

Bladder pain syndrome/interstitial cystitis is a complex pathology often associated with vulvodynia, endometriosis and pelvic floor dysfunctions. Therefore, it is of utmost importance to obtain an accurate evaluation ruling out confusable disease, such as pudendal neuropathy. The optimal approach is a combined treatment oriented not only to treat the bladder, but also the other components responsible for the pain disorder.

 

 

Dis Colon Rectum. 2014 Jun;57(6):733-9.

Is patient diagnosis a risk factor for organ space infection after colorectal resections?

Eskicioglu C1Nelson JRoberts PLMarcello PWRead TEHall JFSchoetz DJRicciardi R.

Abstract

BACKGROUND:

Validated risk adjustment programs do not use patient diagnosis as a potential covariate in the evaluation of organ space infections.

OBJECTIVE:

We hypothesized that patient diagnosis is an important risk factor for organ space infection after colorectal resections.

DESIGN:

We conducted a retrospective cohort study abstracting data from the American College of Surgeons National Surgical Quality Improvement Program from January 2005 through December 2009.

PATIENTS:

Patients who underwent 1 of 3 types of colorectal resections (ileocolostomy, partial colectomy, and coloproctostomy) were identified by the use of Current Procedural Terminology codes. We excluded patients with concomitant formation of diverting or end stoma.

OUTCOME MEASURES:

The primary outcome measured was organ space infection.

ANALYSIS:

Validated risk adjustment models were used with the addition of diagnostic codes.

RESULTS:

We identified 52,056 patients who underwent a colorectal resection of whom 1774 patients developed an organ space infection (3.4%) and 894 (50.2%) returned to the operating room for further surgery. For ileocolostomy, operations for endometriosis (OR, 7.8; 95% CI, 1.7-36.6) and intra-abdominal fistula surgery (OR, 3.0; 95% CI, 1.5-6.0) were associated with increased risk of organ space infection. For partial colectomy, operations for intra-abdominal fistula surgery (OR, 2.3; 95% CI, 1.2-4.3), IBD (OR, 2.5; 95% CI, 1.6-3.8), and bowel obstruction (OR, 1.8; 95% CI, 1.2-2.6) were associated with an increased risk of organ space infection. For coloproctostomy, operations for malignant neoplasm (OR, 2.2; 95% CI, 1.1-4.3) and diverticular bleeding (OR, 3.1; 95% CI, 1.1-9.0) were associated with an increased risk of organ space infection.

LIMITATIONS:

This study was limited by the retrospective study design.

CONCLUSIONS:

After adjustment for National Surgical Quality Improvement Program covariates, intra-abdominal fistula, endometriosis, and diverticular bleeding were the diagnoses associated with the highest risk of organ space infection following colorectal resections.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Jul;178:56-9.

Management of thoracic endometriosis: single institution experience.

Duyos I1López-Carrasco A2Hernández A2Zapardiel I2de Santiago J2.

Abstract

OBJECTIVE:

Thoracic endometriosis is a relatively rare type of endometriosis and includes catamenial pneumothorax, hemothorax and hemoptysis, and presence of intrathoracic endometriotic nodules. We want to clarify and resume the most appropriate management of this pathology.

STUDY DESIGN:

We retrospectively reviewed all the cases of thoracic endometriosis diagnosed and followed up in our Unit from 2005 to 2013. This search revealed five women, with a mean age of 34.5 (26-44). Four had previous history of endometriosis or severe dysmenorrhea. One patient complained of chronic shoulder pain with diaphragmatic implants, another one presented catamenial hemoptysis, and three women suffered from catamenial pneumothorax, with right-side preference.

RESULTS:

Three patients underwent surgery and all of them were treated with GnRH agonists at least during 6 month referring improvement in symptoms. After 1-8 years follow-up, all these patients remain asymptomatic.

CONCLUSION:

The optimal management of thoracic endometriosis needs further evaluation but the combined approach by hormonal therapy and surgery could be the best option.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Jul;178:107-13.

Hysterectomy rates for benign conditions are declining in Lombardy, Italy: 1996-2010.

Parazzini F1Ricci E2Bulfoni G1Cipriani S1Chiaffarino F1Malvezzi M3Frigerio L1.

Abstract

OBJECTIVE:

To analyse the hysterectomy rates (HR) temporal trends for gynecological benign conditions in Lombardy, Northern Italy.

STUDY DESIGN:

Since 1991, discharges from public or private hospitals have been registered in a standard form (Lombardy Region registry). Women aged ≥20 years, residing in Lombardy, who underwent hysterectomy for benign conditions, were included in the study. Admissions were codified according to the ICD-9 and ICD-10. HRs per 1000 women residing in Lombardy, of the same age class, were computed.

RESULTS:

In 1996-2010, 143,045 hysterectomies were performed for benign indications. HR showed a declining trend (average annual percent change (AAPC) -2.9), mainly due to the falling number of total abdominal hysterectomies (AAPC -5.3). The most remarkable decrease was seen in women aged 45-54 years (HR 8.05 in 1996 and 4.83 in 2010). Leiomyoma was the most frequent indication in women aged <55 years, whereas in older patients it was uterine prolapse.

CONCLUSIONS:

In 1996-2010, the frequency of hysterectomy in Lombardy fell markedly. This study confirms the declining trend in abdominal hysterectomies observed in most developed countries, though the surgical approaches to hysterectomy differ in different countries. In particular, in Lombardy the proportion of laparoscopically assisted vaginal hysterectomies, though increasing, is low.

 

Mol Hum Reprod. 2014 Aug;20(8):767-75.

Matrix metalloproteinase-27 is expressed in CD163+/CD206+ M2 macrophages in the cycling human endometrium and in superficial endometriotic lesions.

Cominelli A1Gaide Chevronnay HP1Lemoine P1Courtoy PJ1Marbaix E1Henriet P2.

 

Abstract

Matrix metalloproteinases (MMPs) are key enzymes involved in extracellular matrix remodelling. In the human endometrium, the expression and activity of several MMPs are maximal during the menstrual phase. Moreover, MMPs are thought to be involved in the pathogenesis of endometriosis and cancers, in particular with invasion and metastasis. We recently reported that MMP-27 is a unique MMP with an intracellular retention motif. We investigated the expression and cellular localization of MMP-27 in the cycling human endometrium and in endometriotic lesions. MMP-27 mRNA was detected throughout the menstrual cycle. Despite large interpatient variations, mRNA levels increased from the proliferative to the secretory phase, to peak during the menstrual phase. MMP-27 was immunolocalized in large isolated cells scattered throughout the stroma and around blood vessels: these cells were most abundant at menstruation and were identified by immunofluorescence as CD45(+), CD163(+) and CD206(+) macrophages. CD163(+) macrophages were also abundant in endometriotic lesions, but showed different patterns in ovarian or peritoneal endometriotic lesions (co-labelling for CD206 and MMP-27) and rectovaginal lesions (no co-labelling). In conclusion, MMP-27 is expressed in a subset of endometrial macrophages related to menstruation and in ovarian and peritoneal endometriotic lesions.

 

 

Gynecol Endocrinol. 2014 Aug;30(8):597-9.

Prediction of the therapeutic effect of dienogest in ovarian endometrial cysts using the apparent diffusion coefficient.

Matsuura M1Tamate MTabuchi YTakada STanaka RIwasaki MSaito T.

 

Abstract

The purpose of this study was to investigate whether apparent diffusion coefficient (ADC) mean values can be used for predicting the treatment response in ovarian endometrial cyst patients with dienogest (DNG) administration. Eighteen patients received DNG (2 mg/day, orally) for 60 days, among whom 26 ovarian endometrial cysts were retrospectively identified. Mean ADC values of individual ovarian endometrial cysts were obtained by ADC maps inside the tumor. There was a significant correlation between ADC values and reduction ratio. When calculating the mean ADC values for three groups; more than 50%, 50-25% and less than 25%, ADC values significantly increased with increasing reduction ratio; 2.05 × 10(-3)mm(2)/s, 1.28 × 10(-3)mm(2)/s and 0.94 × 10(-3)mm(2)/s, respectively (p = 0.0180). Multiple regression analysis by reduction ratio (%), ADC mean values (× 10(-3)mm(2)/s), tumor longest diameter (cm) and CA125 (U/ml) revealed that tumor reduction ratio by DNG administration could be predicted by the following equation; R = 19.3 + 24.0x – 0.4y + 0.1z (R: Reduction ratio, x: ADC mean, y: Longest diameter, z: CA125). In conclusion, the ADC mean value is useful for the prediction of the treatment response in ovarian endometrial cyst patients with DNG administration.

 

 

Biomed Res Int. 2014;2014:437962.

Evaluation of the usefulness of the MRI jelly method for diagnosing complete cul-de-sac obliteration.

Kikuchi I1Kuwatsuru R2Yamazaki K2Kumakiri J1Aoki Y1Takeda S1.

Abstract

OBJECTIVE:

We conducted a single-center study to evaluate the usefulness of the magnetic resonance (MR) imaging jelly method for diagnosing endometriosis-associated adhesions in the Pouch of Douglas.

METHODS:

Thirty women with menstrual pain, dyspareunia, and chronic pelvic pain were enrolled in the study. All had been scheduled for laparoscopic surgery on the basis of pelvic and/or ultrasonographic (US) evaluation. All underwent MR imaging both with and without application of US jelly to the vagina and rectum. The images were compared and analyzed postsurgically in a random and blinded fashion by a radiology specialist and a radiology fellow. The radiologists’ interpretations of the images were compared to the surgical findings recorded on DVDs.

RESULTS:

Adhesions in the Pouch of Douglas were found in 21 patients. The sensitivity and specificity of MR imaging without jelly administration were 85.7% and 55.6%, respectively, for the specialist and 81.0% and 55.6%, respectively, for the fellow; with jelly administration, values were 95.2% and 88.9% for the specialist and 90.5% and 66.7% for the fellow. Opacity produced by the jelly increased the sensitivity and specificity for both radiologists.

CONCLUSION:

The MRI jelly method is a potentially useful, beneficial, and simple approach for diagnosing Pouch of Douglas adhesions.

 

 

Eur J Obstet Gynecol Reprod Biol. 2014 Jul;178:128-33

Investigation of diagnostic potentials of nine different biomarkers in endometriosis.

Ozhan E1Kokcu A2Yanik K3Gunaydin M3.

Abstract

OBJECTIVE:

To investigate the diagnostic potentials of the serum levels of nine different biomarkers in endometriosis.

STUDY DESIGN:

In this case-controlled, prospective clinical study, 80 women underwent laparoscopy or laparotomy with a preliminary diagnosis of chronic pelvic pain, severe secondary dysmenorrhea, infertility, pelvic endometriosis or pelvic mass. The 60 women with confirmed pelvic endometriosis constituted the endometriosisgroup, and the other 20 women without endometriosis constituted the control group. Preoperative blood samples were obtained for serum biomarker measurements. Serum levels of nine different serum biomarkers including α-enolase, macrophage migration inhibitory factor, leptin, interleukin-8, anti-endometrial antibody, phosphoinositide dependent protein kinase 1, CA125, syntaxin-5, and laminin-1 were measured concurrently and compared between the control and endometriosis groups, and among control group and endometriosissubgroups including stage I, stage II, stage III and stage IV endometriosis.

RESULTS:

The serum levels of α-enolase, macrophage migration inhibitory factor, leptin, interleukin-8 and antiendometrial antibodies showed a statistically significant difference neither between control and endometriosis groups nor among control group and endometriosis subgroups. The serum levels of CA125, syntaxin-5 and laminin-1 showed a statistically significant difference both between the control and endometriosisgroups (p<0.01) and among control group and endometriosis subgroups (p<0.01). Serum levels of laminin-1 in stage II and IV endometriosis; syntaxin-5 in stage I and II endometriosis; and CA125 in stage III and IV endometriosis were found to have the different levels compared to control group.

CONCLUSIONS:

These findings show that the concurrent measurement of CA125, syntaxin-5 and laminin-1 might be a useful non-invasive test in strengthening the diagnosis of endometriosis and in predicting its severity.

 

 

Int J Surg Case Rep. 2014;5(6):345-6.

Successful obturator nerve repairing: Intraoperative sural nerve graft harvesting in endometrium cancer patient.

Harma M1Sel G2Açıkgöz B3Harma Mİ1.

Abstract

INTRODUCTION:

Intraoperative injury of obturator nerve is a rare complication of gynecologic surgeries, it has been reported especially in patients with endometriosis and genitourinary malignancies. Gynecologic patients undergoing open lymphadenectomy are at increased risk of obturator nerve injury.

PRESENTATION OF CASE:

A 60-year-old woman with FIGO stage II Grade II endometrial adenocarcinoma underwent bilateral pelvic paraaortic lymphadenectomy. During right obturator lymph node dissection, the right obturator nerve was inadvertently transected with Harmonic scalpel sealing system. The graft was used to anastomose epyneurium of distal segment of obturator nerve to its counterpart in the proximal segment with 10-0 prolen suture.

DISCUSSION:

In case of iatrogenic nerve transection, microsurgical end to end tension-free coaptation is advocated. In case of the obturator nerve is fixed and because of the thermal injury end to end alignment can not be achieved, nerve grafting is necessary.

CONCLUSION:

According to our knowledge, successful immediate grafting of iatrogenically damaged obturator nerve during pelvic lymphadenectomy in our patient is the third report of such a case, but also it has a unique feature of being the first obturator nerve repairing case after dissected with tissue sealing system which causes large sealed area that does not make it possible to make end-to-end anastomosis without nerve harvesting.

 

 

J Clin Endocrinol Metab. 2014 Aug;99(8):2795-803.

Metformin inhibits StAR expression in human endometriotic stromal cells via AMPK-mediated disruption of CREB-CRTC2 complex formation.

Xu JN1Zeng CZhou YPeng CZhou YFXue Q.

Abstract

CONTEXT:

Endometriosis is an estrogen-dependent disease affecting reproductive women. Metformin could have a therapeutic effect on endometriosis through regulation of local estrogen production.

OBJECTS:

The aim of this study was to investigate the molecular and cellular mechanism by which metformin regulates StAR expression in human endometriotic stromal cells (ESCs).

METHODS:

ESCs derived from ovarian endometriomas were cultured with metformin and prostaglandin E2 (PGE2). StAR mRNA was measured by quantitative PCR; pregnenolone, progesterone, and estrogen production were measured by ELISA kits; steroidogenic acute regulatory protein (StAR), AMP-activated protein kinase, cAMP response element binding protein (CREB), and CREB-regulated transcription coactivator 2 (CRTC2) protein expression were measured by Western blot assay; and CRTC2 translocation and its association with CREB were assessed by coimmunoprecipitation assay and CRTC2-CREB complex binding by a chromatin immunoprecipitation assay.

RESULTS:

1) StAR mRNA levels in ESCs are 264 times higher than those in endometrial cells. 2) Metformin downregulates the StAR mRNA expression (maximum 31.7%) stimulated by PGE2 (2.4-fold) in ESCs. 3) PGE2 induces CRTC2 translocation and enhances its association with CREB to form a transcription complex that binds to the StAR promoter region. 4) Metformin prevents the nuclear translocation of CRTC2 by increasing AMP-activated protein kinase phosphorylation. This inhibits transcription of StAR by disrupting formation of the CREB-CRTC2 complex, involved in activation of the StAR promoter cAMP response element.

CONCLUSIONS:

We have demonstrated a detailed mechanistic analysis of StAR expression regulated by metformin in ESCs. Our data highlight a role for CRTC2 in the mechanism by which metformin inhibits StAR expression.

 

Eur J Pain. 2015 Jan;19(1):103-10.

Impact of surgical excision of lesions on pain in a rat model of endometriosis.

Alvarez P1Giudice LCLevine JD.

Abstract

BACKGROUND:

Chronic pain is the most common and disabling feature of endometriosis. Surgical excision of endometriosis lesions provides relief but pain relapse is common. Studies in a preclinical model of endometriosismight help to unravel the role of the ectopic lesions as the source of pain. Thus, we evaluated the impact of lesion excision on mechanical hyperalgesia in a preclinical model of endometriosis pain.

METHODS:

Endometriosis was induced by implanting autologous uterine tissue onto the gastrocnemius muscle. Surgical excision or aspiration drainage of the cystic lesion was performed at different times post-implant and mechanical nociceptive thresholds were assessed at the site of the lesion.

RESULTS:

Lesions at 2, 8 and 16 weeks post-implant produced mechanical hyperalgesia of similar magnitude (n = 6/group). Excision of lesions (n = 6/group) produced a longer inhibition, with a magnitude and time course depending upon the timing of excision. Excision at 2 and 8 weeks produced a rapid onset marked attenuation of hyperalgesia, which returned to pre-excision values by post-surgical week 3. In contrast, excision of the lesion at 16 weeks produced a peak of inhibition of hyperalgesia 2 weeks post-excision, but then the inhibition was sustained. Aspiration of fluid from cysts in the lesions briefly attenuated mechanical hyperalgesia (n = 6/group).

CONCLUSIONS:

In this preclinical model, we demonstrate that endometriosis pain is alleviated by surgical excision of the ectopic lesion or drainage of its cysts, providing support for the clinical observation that endometriosis pain is dependent upon the ongoing presence of the lesions.

 

 

Fertil Steril. 2014 Jul;102(1):167-177

CD26/DPPIV down-regulation in endometrial stromal cell migration in endometriosis.

Tan CW1Lee YH2Tan HH3Lau MS3Choolani M4Griffith L5Chan JK6.

Abstract

OBJECTIVE:

To test the hypothesis that endometrial stromal cells (ESCs) in endometriosis exhibit increased cell motility under hypoxia.

DESIGN:

Prospective case-control study.

SETTING:

University research laboratory.

PATIENT(S):

Women with endometriosis (n = 18) or benign gynecological disease (n=19).

INTERVENTION(S):

Eutopic ESCs were cultured under normoxia (20% O2) or hypoxia (6.5% O2), and migration and invasion capacity assayed, with pathway-focused polymerase chain reaction (PCR) array and ELISAs performed. CD26/dipeptidyl peptidase IV (DPPIV) expression was determined by flow cytometric analysis and enzymatic activity assay. The ESCs supplemented with Diprotin A (CD26 inhibitor), stromal cell-derived factor-1α, or AMD3100 (C-X-C motif receptor 4; CXCR4 blocker) were assayed for their migratory potential.

MAIN OUTCOME MEASURE(S):

Endometrial stromal cell migration and invasion under hypoxia.

RESULT(S):

Endometriotic ESCs showed significantly higher migration and invasion through collagen gels under hypoxia compared with nonendometriotic ESCs. The PCR array revealed down-regulation of the migration inhibitor CD26/DPPIV and up-regulation of angiogenic factors (vascular endothelial growth factor A, C-X-C motif Ligand 6; CXCL6) in endometriotic ESCs under hypoxia. The CD26/DPPIV surface expression and activity as well as angiogenic protein secretions suggested that the molecular mechanisms underlying aberrant migratory and angiogenic behavior in endometriotic ESCs. A combinatorial treatment with diprotin A and stromal cell-derived factor-1α effectively enhanced migration and invasion preferentially in endometriotic ESCs cultured hypoxically.

CONCLUSION(S):

Loss of CD26/DPPIV under hypoxia and the subsequent increase in migratory and angiogenic factors may favor conditions for lesion development in endometriosis.

 

 

Fertil Steril. 2014 Jul;102(1):151-159

Dynamics of nitric oxide, altered follicular microenvironment, and oocyte quality in women with endometriosis.

Goud PT1Goud AP2Joshi N3Puscheck E3Diamond MP4Abu-Soud HM3.

Abstract

OBJECTIVE:

To study follicular microenvironment in terms of free radical dynamics, oocyte quality, and assisted reproductive technology (ART) outcomes among women with (group A) and without (group B) endometriosis.

DESIGN:

Prospective cohort study.

SETTING:

University ART center.

PATIENT(S):

Women with and without endometriosis undergoing ART (n=28).

INTERVENTION(S):

Follicular fluid (FF), granulosa cells (GCs), immature oocytes (IOs), and ART data on sibling cohort oocytes in groups A and B were compared.

MAIN OUTCOME MEASURE(S):

ART live birth outcomes, maturation, and aging among in vitro matured (IVM) oocytes, nitrate levels in FF, and nitrotyrosine (NT) footprints and apoptosis in the GCs.

RESULT(S):

Clinical characteristics and ART live birth outcomes were no different between groups A and B. Women from group A had significantly lower peak serum E2 (2,068.8±244.6 pg/mL vs. 2,756.2±205.0 pg/mL) and higher apoptosis (80.0% vs. 22.2%) and NT staining (70.0% vs. 22.2%) in GCs compared with group B. Fewer IOs underwent IVM to MII (0.6±0.3) in group A compared with group B (1.4±0.2). IVM oocytes had significantly higher incidence of cortical granule loss (83.3% vs. 24.0%) and spindle disruption (66.7% vs. 16.0%) and higher zona pellucida dissolution timing (133.8±9.4 s vs. 90.5±5.8 s) in group A compared with group B. FF nitrate levels were significantly higher in women who failed to conceive in group A (478.2±43.1 nmol/L) compared with those that did conceive (173.3±19.0 nmol/L).

CONCLUSION(S):

Increased protein nitration, GC apoptosis, resistance to IVM, and oocyte aging indicate the involvement of oxidative dysregulation of NO in the pathophysiology of altered follicular milieu and poor oocyte quality in women with endometriosis.

 

 

Int J Gynaecol Obstet. 2014 Jul;126(1):45-9

Hysterectomy trends over a 9-year period in an endoscopic teaching center.

Schollmeyer T1Elessawy M2Chastamouratidhs B1Alkatout I1Meinhold-Heerlein I3Mettler L1Jonat W1Weigel MT1.

Abstract

OBJECTIVE:

To investigate trends in the performance of hysterectomy at a single certified endoscopic teaching center.

METHODS:

Data were collected retrospectively from 953 patients who underwent hysterectomy between 2002 and 2010 for benign indications at UKSH, Germany. Preoperative risk scores were assigned to patients.

RESULTS:

The most frequent indications for hysterectomy were uterine myoma, adenomyosis, prolapse, endometrial hyperplasia, menstrual disorders, and endometriosis. The shortest operating time was recorded for vaginal hysterectomy (VH) and the longest for laparoscopically assisted VH (LAVH). The average uterine weight was highest for abdominal hysterectomy (AH) and lowest for VH. The major postoperative complication rate was 11.8% for laparoscopic supracervical hysterectomy (LSH) and 23.5% for AH. The highest intraoperative complication rate occurred with AH (46.4%) and the lowest with total laparoscopic hysterectomy (TLH; 3.6%). The minor postoperative complication rate was 5.9%. The mean preoperative score was 1.09±1.51 for AH, 0.75±0.96 for VH, 1.04±1.30 for LSH, 1.0±1.40 for LAVH, and 1.38±1.52 for TLH.

CONCLUSION:

Laparoscopic hysterectomies have become more common and were associated with decreased complication rates, despite the higher preoperative risk score of these patients.

 

 

Int J Surg Pathol. 2015 Apr;23(2):134-9.

Hepatic uterus-like mass misdiagnosed as hepatic abscess.

Sopha SC1Rosado FG2Smith JJ3Merchant NB4Shi C4.

Abstract

BACKGROUND:

Hepatic endometriosis/uterus-like mass is rare and may be overlooked during hepatic cyst workups. We report a case of uterus-like mass, misdiagnosed as hepatic abscess.

CASE REPORT:

A 47-year-old woman developed abdominal pain and vomiting. Infectious colitis with hepatic abscess was diagnosed, and remained antibiotic-refractory. Fine-needle aspiration and core biopsies showed benign contents. The patient presented to our institution with symptoms and normal blood work. Laparoscopic excision demonstrated a 1.4-cm cyst composed of endometrial glands (estrogen receptor+ and progesterone receptor+) and stroma (CD10+) with smooth muscle actin (SMA+), arranged in an organoid fashion. The patient, status-post hysterectomy, had no history or symptoms of endometriosis.

CONCLUSION:

This rare case illustrates the merit of considering uterus-like mass/endometriosis in the differential diagnosis of antibiotic-refractory hepatic cysts. Cyst heterogeneity may confound needle biopsy. We report the first instance of a hepatic uterus-like mass, with a review of related entities, postulated histogenesis, and important clinical associations.

 

 

Radiology. 2014 Oct;273(1):117-24.

Bowel endometriosis: preoperative diagnostic accuracy of 3.0-T MR enterography–initial results.

Rousset P1Peyron NCharlot MChateau FGolfier FRaudrant DCotte EIsaac SRéty FValette PJ.

Abstract

PURPOSE:

To prospectively determine the accuracy of 3.0-T magnetic resonance (MR) enterography in the preoperative assessment of deep infiltrating endometriosis (DIE) lesions located in the bowel above the rectosigmoid junction.

MATERIALS AND METHODS:

Institutional review board approval for this study was obtained, and each patient gave written informed consent. Over 18 months, patients with known pelvic DIE who were scheduled for surgery were recruited. Consecutive patients suspected of having bowel endometriosis above the rectosigmoid junction underwent 3.0-T MR enterography. Two blinded readers independently performed a systematic analysis of nine bowel segments above the rectosigmoid junction. MR images were compared with surgical and pathologic findings. Efficacy parameters were calculated with 95% confidence intervals (CIs). Interobserver agreement was assessed with κ statistics.

RESULTS:

Among the 43 patients enrolled in this study, 33 underwent surgery and were included in the final analyses. Sixteen (48%) patients had bowel DIE lesions located above the rectosigmoid junction at surgery and histopathologic examination. Twenty-six lesions were analyzed, including four ileal, two ileocecal, three cecal, three appendicular, and 14 sigmoid colon lesions. For the diagnosis of these lesions, MR imaging showed sensitivities of 92% (95% confidence interval [CI]: 81.7, 100) for reader 1 and 96% (95% CI: 87.1, 100) for reader 2 and specificities of 100% (95% CI: 98.8, 100) for both readers. The κ value was 0.97.

CONCLUSION:

These results show 3.0-T MR enterography is accurate in the preoperative diagnosis and mapping of bowel DIE lesions located above the rectosigmoid junction. Online supplemental material is available for this article.

 

 

J Gynecol Obstet Biol Reprod (Paris). 2014 Jun;43(6):431-42.

Urinary functional disorders bound to deep endometriosis and to its treatment: review of the literature.

Campin L1Borghese B2Marcellin L3Santulli P3Bourret A4Chapron C3.

 

Abstract

Lower urinary tract disorders in case of deep endometriosis are common (up to 50% of patients), although often masked by pelvic pain. They result from damage to the pelvic autonomic nervous system by direct infiltration of these structures by endometriotic lesions or surgical trauma (especially in resection of the uterosacral ligaments, rectum or vagina). These are mainly sensory disturbances and bladder voiding dysfunction. They impact quality of life and could be responsible for long-term complications (recurrent urinary tract infections on a persistent residual urine or pelvic floor disorders due to chronic thrusting). It is therefore important to diagnose and treat early these troubles by well-conducted interviews or standardized questionnaires. Different drug treatments have been proposed, such as cholinergics or prokinetics, but their effectiveness has not been demonstrated yet. Neuromodulation of the superior hypogastric plexus for treatment of refractory atonic bladder with persistent urinary retention after surgery seems promising but should be confirmed by further studies. To date, standard treatment of urinary retention after surgery remains self-catheterization. In terms of prevention, surgical nerve sparing techniques have been developed in order to minimize intraoperative injury of pelvic nerve plexus and reduce postoperative morbidity.

 

 

Histol Histopathol. 2014 Oct;29(10):1217-33.

The biological role of Treg cells in ectopic endometrium homeostasis.

Basta P1Koper K2Kazmierczak W3Wisniewski M4Makarewicz A5Dutsch-Wicherek M3Kojs Z6Popiela TJ6Slusarz R7Dubiel M8Wicherek L9.

 

Abstract

Although retrograde menstruation is observed in up to 90% of women, endometriosis actually develops in only 15% of women. There is considerable evidence in the literature that ectopic endometrial cells are able to evade immune surveillance and that the immune response in the microenvironment of ectopic lesions is limited. Endometriosis develops when a deficiency in the local immune response has been generated, and progression of the disease is related to the intensity of this process. Over the last couple of decades it has been well known that T regulatory lymphocytes (Tregs) play a crucial role in controlling a variety of physiological and pathological immune responses. In this review we have focused on the physiological alteration of Treg cell infiltration into the endometrium during the reproductive processes of women. We discuss how a disturbance in Treg cell expansion is involved in generating such pathological processes as miscarriage and ectopic pregnancy development. We hypothesize about the role Treg cells might play in the survival of endometriosis foci in ectopic localization and in the evasion of such lesions from host immune surveillance.

 

 

Lung. 2014 Aug;192(4):583-7.

Thoracic endometriosis-related pneumothorax distinguished from primary spontaneous pneumothorax in females.

Haga T1Kataoka HEbana HOtsuji MSeyama KTatsumi KKurihara M.

Abstract

PURPOSE:

Thoracic endometriosis-related pneumothorax (TERP) is a secondary condition specific for females, but in a clinical setting, TERP often is difficult to distinguish from primary spontaneous pneumothorax (PSP) based on a relationship between the dates of pneumothorax and menstruation. The purpose of this study was to clarify the clinical features of TERP compared with PSP.

METHODS:

We retrospectively reviewed the clinical and histopathological files of female patients with pneumothorax who underwent video-assisted thoracoscopic surgery in the Pneumothorax Research Center during the 6-year period from January 2005 to December 2010. We analyzed the clinical differences between TERP and PSP.

RESULTS:

The study included a total of 393 female patients with spontaneous pneumothorax, of whom 92 (23.4 %) were diagnosed as having TERP and 33.6 % (132/393) as having PSP. We identified four factors (right-sided pneumothorax, history of pelvic endometriosis, age ≥31 years, and no smoking history) that were statistically significant for predicting TERP and assigned 6, 5, 4, and 3 points, respectively, to establish a scoring system with a calculated score from 0 to 18. The cutoff values of a calculated score ≥12 yielded the highest positive predictive value (86 %; 95 % confidence interval (CI) 81.5-90.5 %) for TERP and negative predictive value (95.2 %; 95 % CI 92.3-98 %) for PSP.

CONCLUSIONS:

TERP has several distinct clinical features from PSP. Our scoring system consists of only four clinical variables that are easily obtainable and enables us to suspect TERP in female patients with pneumothorax.

 

 

Expert Opin Pharmacother. 2014 Jun;15(8):1153-79.

Triptorelin for the treatment of endometriosis.

Leone Roberti Maggiore U1Scala CRemorgida VVenturini PLDel Deo FTorella MColacurci NSalvatore SFerrari SPapaleo ECandiani MFerrero S.

Abstract

INTRODUCTION:

Over the past 30 years, gonadotropin-releasing hormone agonists (GnRH-a) have been used to induce a hypoestrogenic status in women with endometriosis with the aim to cause an improvement in pain symptoms similar to that observed after menopause. Triptorelin is one of the most commonly used GnRH-a.

AREAS COVERED:

This review offers an explanation of the mechanism of action, of the pharmacokinetics and pharmacodynamics of triptorelin and gives the readers a complete overview of the studies on the clinical efficacy, tolerability and safety of this agent in patients with endometriosis.

EXPERT OPINION:

The studies reviewed in the current manuscript demonstrate the efficacy of triptorelin in improving pain symptoms caused by endometriosis. Further, this effect is confirmed by the reduction in the volume of the endometriotic nodules during treatment. Future research should evaluate whether the pre-operative administration of triptorelin prior to surgical excision of endometriomas may be useful in preserving the ovarian reserve.

 

Can Assoc Radiol J. 2014 Nov;65(4):327-34.

Outside the inside: a review of soft-tissue abnormalities seen on thoracoabdominal computed tomography.

Frank SJ1Friedman S1Flusberg M1Wolf EL1Stein MW2.

 

Abstract

In this review, we illustrate the computed tomographic features of thoracoabdominal soft-tissue abnormalities, which may be easily overlooked and often can provide important information regarding systemic processes. Examples include necrotizing fasciitis, heterotopic ossification, fat necrosis, benign and malignant neoplasms, endometriosis, and collagen vascular disease as well as systemic and congenital pathology.

 

 

Environ Res. 2014 Jul;132:328-33.

Metal status in human endometrium: relation to cigarette smoking and histological lesions.

Rzymski P1Rzymski P2Tomczyk K2Niedzielski P3Jakubowski K3Poniedziałek B4Opala T2.

 

Abstract

Human endometrium is a thick, blood vessel-rich, glandular tissue which undergoes cyclic changes and is potentially sensitive to the various endogenous and exogenous compounds supplied via the hematogenous route. As recently indicated, several metals including Cd, Pb, Cr and Ni represent an emerging class of potential metalloestrogens and can be implicated in alterations of the female reproductive system including endometriosisand cancer. In the present study, we investigated the content of five metals: Cd, Cr, Ni, Pb and Zn in 25 samples of human endometrium collected from Polish females undergoing diagnostic or therapeutic curettage of the uterine cavity. The overall mean metal concentration (analyzed using microwave induced plasma atomic emission spectrometry MIP-OES) decreased in the following order: Cr>Pb>Zn>Ni>Cd. For the first time it was demonstrated that cigarette smoking significantly increases the endometrial content of Cd and Pb. Concentration of these metals was also positively correlated with years of smoking and the number of smoked cigarettes. Tissue samples with recognized histologic lesions (simple hyperplasia, polyposis and atrophy) were characterized by a 2-fold higher Cd level. No relation between the age of the women and metal content was found. Our study shows that human endometrium can be a potential target of metal accumulation within the human body. Quantitative analyses of endometrial metal content could serve as an additional indicator of potential impairments of the menstrual cycle and fertility.

 

 

 

Forensic Sci Int. 2014 Jul;240:e25-8.

Sudden death of a middle aged woman with a series of undiagnosed gynaecologic diseases.

Hikiji W1Hayashi K2Fukunaga T2.

 

Abstract

Gynaecologic diseases unrelated to pregnancy are not generally associated with sudden death, which limits the number of case reports published in the field of forensic medicine. Presented in this paper is a fatal case in a middle aged woman with an early stage endometrial cancer and a series of gynaecologic diseases, in whom such typical features of sudden death were not applicable. Forensic autopsy revealed the hypoplasia of left circumflex coronary artery, Stage 1B endometrial cancer, endometriosis, polycystic ovary syndrome (PCOS) and micro pituitary adenoma, whereas histochemical analyses confirmed hyperprolactinemia and hyperestradiolemia. It was considered that the hypoplasia of coronary artery, chronic anaemia and electrolyte imbalance due to endometrial cancer all collaborated to induce acute cardiac failure. The association between prolactinoma, PCOS and endometrial cancer was also suggested, though they are rarely observed synchronously. It was speculated that the deceased had been anaemic for a substantial period of time and lacked clear subjective symptoms, which made the antemortem diagnosis of her underlying diseases difficult. Forensic pathologists must always consider the possibility of gynaecologic diseases taking significant part in a fatal cause of reproductive-aged women.

 

 

Fertil Steril. 2014 Jul;102(1):264-71.

Lipoxin A4 regulates expression of the estrogen receptor and inhibits 17β-estradiol induced p38 mitogen-activated protein kinase phosphorylation in human endometriotic stromal cells.

Chen S1Wu RF2Su L1Zhou WD1Zhu MB1Chen QH3.

Abstract

OBJECTIVE:

To study the role of lipoxin A4 (LXA4) in endometriosis.

DESIGN:

Molecular analysis in human samples and primary human endometriotic stromal cells (ESCs).

SETTING:

University hospital.

PATIENT(S):

Forty-nine premenopausal women (30 patients with endometriosis and 19 controls).

INTERVENTION(S):

Normal and ectopic endometrial biopsies obtained during surgery performed during the proliferative phase of the menstrual cycle; ESCs used for in vitro studies.

MAIN OUTCOME MEASURE(S):

Levels of LXA4 measured by enzyme-linked immunosorbent assay (ELISA); mRNA levels of the estrogen receptor (ER), progestogen receptor (PR), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR); and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation evaluated by Western blotting.

RESULT(S):

The LXA4 expression level decreased in ectopic tissue as well as ERα and PR, although the expression of ERβ increased in ectopic endometrium compared with the controls. Investigations with correlation analysis revealed the expression of LXA4 was positively correlated with ERα and negatively correlated with ERβ in vivo. Moreover, administering LXA4 could augment ERβ expression in ESCs and inhibit the 17β-estradiol-induced phosphorylation of p38 MAPK very likely through ERβ.

CONCLUSION(S):

Our findings indicate that LXA4 regulates ERβ expression and inhibits 17β-estradiol-induced phosphorylation of p38 MAPK, very likely through ERβ in ESCs.

 

 

Fertil Steril. 2014 Jul;102(1):160-166.

Laparoscopy for ureteral endometriosis: surgical details, long-term follow-up, and fertility outcomes.

Uccella S1Cromi A2Casarin J2Bogani G2Pinelli C2Serati M2Ghezzi F2.

Abstract

OBJECTIVE:

To evaluate perioperative details, long-term outcomes, and postsurgical fertility in case of laparoscopic ureterolysis for deep endometriosis.

DESIGN:

Retrospective analysis of prospectively collected data.

SETTING:

Academic research center.

PATIENT(S):

One hundred nine consecutive women who underwent laparoscopic ureterolysis for deep endometriosis.

INTERVENTION(S):

Laparoscopic excision of ureteral endometriosis (ureteral shaving was attempted in all cases).

MAIN OUTCOME MEASURE(S):

Perioperative details, long-term outcomes, fertility rates, and need for secondary surgery, stratifying on presence/absence of hydronephrosis. Predictors of longer operative time, pain recurrence, and fertility were also investigated.

RESULT(S):

No conversion to open surgery was necessary. Intraoperative ureteral injury occurred in one case (0.9%). Nine women (8.3%) underwent ureteral stenting. Eight cases (7.3%) of mild postoperative complications were registered; no case of severe complications or postoperative ureteral fistula occurred. An increase was observed in the risk of short-/long-term adverse outcomes, according to the grade of preoperative hydronephrosis. Of the 80 women with available follow-up data, secondary ureteral procedures were necessary in 5 women (6.3%), whereas 22 patients (27.5%) had recurrence of endometriosis symptoms. Among the 36 women who wished to conceive, a total of 26 pregnancies were registered in 20 women (55.6%). The miscarriage rate was 15.6%. Hydronephrosis grade≥2 was independently associated with longer operative time and higher rate of symptoms recurrence. Adjuvant hormonal therapy after ureterolysis was the only independent factor associated with lower fertility rates.

CONCLUSION(S):

Laparoscopic ureterolysis is a safe procedure, with encouraging pregnancy rates and satisfactory long-term results. However, hydronephrosis grade≥2 is associated with worse outcomes.

 

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