Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
Case Rep Obstet Gynecol. 2015;
Endometrial stromal sarcoma arising in colorectal endometriosis: a case report and review of the literature.
Extrauterine endometrial stromal sarcoma (ESS) arising in endometriosis is extremely rare, particularly in the colorectum. It should always be included in the differential diagnosis of primary tumors originating from gastrointestinal tract in females, given that preoperative endoscopical biopsy may reveal no specific changes. We reported a case of ESS arising in colorectal endometriosis and reviewed the previous 7 cases reported in the English literature. Our patient, who was unavailable for tumor resection and refused further adjuvant therapy, played a role in representing the natural history of low-grade extragenital ESS. This case was the only death from ESS arising in colorectal endometriosis.
Ugeskr Laeger. 2015 Feb 2;177(6
Intussusception of the appendix.
Intussusception of the appendix is a rare condition with an incidence of approximately 0.01%. In adults, the lead point for the intussusception is most frequently endometriosis, whereas in children, acute inflammation of the appendix is usually the cause (76%). This case report presents a 41-year-old woman who was referred to hospital care primarily due to blood in her stool and a 1 × 3 cm polypous tumour in her caecum, observed during colonoscopy. She had no gynaecologic history and a normal exam. A right-sided hemicolectomy was performed and pathology showed endometriosis and acute and chronic inflammation.
Rev Assoc Med Bras (1992). 2014 Nov-Dec;60(6):560-4.
Endometriosis is an important cause of pelvic pain in adolescence.
Andres Mde P1, Podgaec S2, Carreiro KB3, Baracat EC4.
despite endometriosis being a common disease, where early detection is key to preventing its progression, it is a condition often overlooked in adolescents. The aim of this study was to report the clinical characteristics of adolescent patients with endometriosis monitored in a tertiary hospital.
a retrospective study of 394 patients undergoing surgery with a histological diagnosis of endometriosis at the Endometriosis Division of the Gynecology Department at the Hospital das Clínicas of the University of São Paulo Medical School from 2008 to 2013. 21 adolescents were included (aged under 21 years).
the age ranged from 17.95 ± 1.48 years, the average time for diagnostic confirmation was 2.96 ± 2.93 years, and the age at the onset of symptoms was 15.28 ± 3.03 years on average. The sites affected were ovarian (38%), peritoneal (47.6%) and retrocervical (23.8%). Dysmenorrhea was found in 80.9 % of adolescents (severe in 33.3% of cases) and chronic pelvic pain in 66.6%.
endometriosis in adolescents is an important differential diagnosis from pelvic pain and ovarian cysts, mainly among those with no response to conventional treatment. The main forms of involvement are peritoneal and ovarian. Despite the onset of symptoms in adolescence and advances in imaging methods, the diagnosis of this disease is still delayed.
W V Med J. 2014 Nov-Dec;110(6):36-8.
A large mediastinal mass in a 33 year old patient.
Ison D, Clarke R, Black T, Yung M, Kiev J.
Mediastinal masses are commonly found during the evaluation of other illnesses. During gynecologic evaluation for suspected endometriosis, a large asymptomatic intrathoracic mass was discovered in the patient presented. After pre-operative evaluation, the patient underwent thoracotomy with removal of a mature, cystic teratoma invading the pericardium. Invasion of the pericardium is rarely seen with these lesions. The diagnosis of teratoma is difficult to make based solely on radiologic or clinical findings and must be confirmed at pathology for final diagnosis.
Int J Mol Med. 2015 Apr;35(4):1081-7.
BAD-mediated apoptotic pathway is associated with human cancer development.
Stickles XB1, Marchion DC1, Bicaku E1, Al Sawah E1, Abbasi F1, Xiong Y1, Bou Zgheib N1, Boac BM1, Orr BC1, Judson PL1, Berry A1, Hakam A2, Wenham RM1, Apte SM1, Berglund AE3, Lancaster JM1.
The malignant transformation of normal cells is caused in part by aberrant gene expression disrupting the regulation of cell proliferation, apoptosis, senescence and DNA repair. Evidence suggests that the Bcl-2 antagonist of cell death (BAD)-mediated apoptotic pathway influences cancer chemoresistance. In the present study, we explored the role of the BAD-mediated apoptotic pathway in the development and progression of cancer. Using principal component analysis to derive a numeric score representing pathway expression, we evaluated clinico-genomic datasets (n=427) from corresponding normal, pre-invasive and invasive cancers of different types, such as ovarian, endometrial, breast and colon cancers in order to determine the associations between the BAD-mediated apoptotic pathway and cancer development. Immunofluorescence was used to compare the expression levels of phosphorylated BAD [pBAD (serine-112, -136 and -155)] in immortalized normal and invasive ovarian, colon and breast cancer cells. The expression of the BAD-mediated apoptotic pathway phosphatase, PP2C, was evaluated by RT-qPCR in the normal and ovarian cancer tissue samples. The growth-promoting effects of pBAD protein levels in the immortalized normal and cancer cells were assessed using siRNA depletion experiments with MTS assays. The expression of the BAD-mediated apoptotic pathway was associated with the development and/or progression of ovarian (n=106, p<0.001), breast (n=185, p<0.0008; n=61, p=0.04), colon (n=22, p<0.001) and endometrial (n=33, p<0.001) cancers, as well as with ovarian endometriosis (n=20, p<0.001). Higher pBAD protein levels were observed in the cancer cells compared to the immortalized normal cells, whereas PP2C gene expression was lower in the cancer compared to the ovarian tumor tissue samples (n=76, p<0.001). The increased pBAD protein levels after the depletion of PP2C conferred a growth advantage to the immortalized normal and cancer cells. The BAD-mediated apoptotic pathway is thus associated with the development of human cancers likely influenced by the protein levels of pBAD.
PLoS One. 2015 Feb 6;10(2):e0116977.
Somatic copy number alterations associated with Japanese or endometriosisin ovarian clear cell adenocarcinoma.
Okamoto A1, Sehouli J2, Yanaihara N1, Hirata Y1, Braicu I2, Kim BG3, Takakura S1, Saito M1, Yanagida S1, Takenaka M1, Yamaguchi N1, Morikawa A1, Tanabe H1, Yamada K1, Yoshihara K4, Enomoto T4, Itamochi H5, Kigawa J5, Matsumura N6, Konishi I6, Aida S7, Aoki Y8, Ishii N8, Ochiai K1, Akiyama T7, Urashima M9.
When compared with other epithelial ovarian cancers, the clinical characteristics of ovarian clear cell adenocarcinoma (CCC) include 1) a higher incidence among Japanese, 2) an association with endometriosis, 3) poor prognosis in advanced stages, and 4) a higher incidence of thrombosis as a complication. We used high resolution comparative genomic hybridization (CGH) to identify somatic copy number alterations (SCNAs) associated with each of these clinical characteristics of CCC. The Human Genome CGH 244A Oligo Microarray was used to examine 144 samples obtained from 120 Japanese, 15 Korean, and nine German patients with CCC. The entire 8q chromosome (minimum corrected p-value: q = 0.0001) and chromosome 20q13.2 including the ZNF217 locus (q = 0.0078) were amplified significantly more in Japanese than in Korean or German samples. This copy number amplification of the ZNF217 gene was confirmed by quantitative real-time polymerase chain reaction (Q-PCR). ZNF217 RNA levels were also higher in Japanese tumor samples than in non-Japanese samples (P = 0.027). Moreover, endometriosis was associated with amplification of EGFR gene (q = 0.047), which was again confirmed by Q-PCR and correlated with EGFR RNA expression. However, no SCNAs were significantly associated with prognosis or thrombosis. These results indicated that there may be an association between CCC and ZNF217 amplification among Japanese patients as well as between endometriosis and EGFR gene amplifications.
J Minim Invasive Gynecol. 2015 May-Jun;22(4):648-52.
The use of barbed suture for bladder and bowel repair.
To describe the laparoscopic repair of bladder and bowel injuries using barbed suture and review postoperative outcomes.
Retrospective medical chart review (Canadian Task Force classification II-3).
Large academic medical institution.
Thirty-three women who underwent laparoscopic repair of the bladder and/or bowel wall using barbed suture between January 2009 and July 2013.
MEASUREMENT AND MAIN RESULTS:
The patients underwent a total of 9 cystotomies (27.3%), 7 enterotomies (21.2%), 4 bladder seromuscular injuries (12.1%), 12 bowel seromuscular injuries (36.4%), and 1 bladder and bowel seromuscular injury (3.0%). Of the 33 injuries, 17 (51.5%) were intentional in the setting of bladder or bowel endometriosis nodule excision, whereas the other 16 (48.5%) were accidental and occurred at the time of lysis of adhesions. Thirteen of 14 bladder injuries (92.9%) were at the dome, and 1 injury (7.1%) was at the trigone. Fifteen of 20 bowel injuries (75%) were rectal, 3 (15%) were on the colon, and 2 (10%) were on the small intestine. Cystotomies ranged in length from 1 to 5 cm, and enterotomies ranged from 1.5 to 6 cm. All bladder and bowel seromuscular injuries were repaired using a single layer of barbed suture. Twelve full-thickness bladder or bowel wall defects (75%) were repaired using 2 layers of barbed suture, and 4 defects (25%) were repaired using a layer of barbed suture and a layer of a running or interrupted smooth delayed absorbable suture. Duration of follow-up ranged from 1 month to 15 months. There were no major complications. Only 1 patient who had undergone a large enterotomy repair developed constipation secondary to a mild rectal stricture diagnosed 3 months postoperatively. Symptoms of constipation since resolved spontaneously in that patient.
Barbed suture provides adequate tension-free bladder and bowel repair. No major complications have been encountered; therefore, the use of barbed suture for the repair of bladder or bowel defects seems feasible and safe.
Hum Reprod. 2015 Apr;30(4):925-36.
Estrogen induced changes in uterine brain-derived neurotrophic factor and its receptors.
Wessels JM1, Leyland NA1, Agarwal SK2, Foster WG3.
Are brain-derived neurotrophic factor (BDNF) and its receptors, NTRK2, NGFR and SORT1, regulated by ovarian steroids in the uterus?
BDNF and its low affinity receptor, nerve growth factor receptor (NGFR), are regulated by estradiol in the uterus.
WHAT IS KNOWN ALREADY:
Recent studies have revealed a central role for neurotrophins in placental development, endometrial stem cell neurogenesis, endometrial carcinoma and endometriosis. Complex signaling pathways involving BDNF and its receptors are regulated by ovarian hormones in the brain, however their expression and regulation in the uterus is poorly defined.
STUDY DESIGN, SIZE, DURATION:
This experimental animal study involved a total of 80 mice.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Female C57BL/6 mice (n = 50) were monitored daily for estrous cycle stage, and uterine horns were collected. A second group of mice (n = 30) were ovariectomized and given estradiol, progesterone, estradiol + progesterone, or saline for 4 days. Uterine expression of BDNF and its receptors were quantified by real-time PCR and western blot, and localized using immunohistochemistry.
MAIN RESULTS AND THE ROLE OF CHANCE:
During the estrous cycle, expression of BDNF, NTRK2 and SORT1 remained constant, while NGFR declined 11-fold from pro-estrus through to diestrus (P = 0.005). In ovariectomized mice, estradiol treatment increased uterine expression of mature BDNF greater than 6-fold (P = 0.013, 25 kDa; P = 0.003, 27 kDa), pro-BDNF 5-fold (P = 0.041, 37 kDa band; P = 0.046, 40 kDa band), and NGFR 5-fold (P < 0.001) when compared with other treatments. NTRK2 and SORT1 were unaffected by ovarian hormones. NGFR was primarily localized in epithelial cells in mice in diestrus or in ovariectomized mice treated with progesterone (P ≤ 0.001; P ≤ 0.001, respectively). In contrast, NGFR switched to a stromal localization in ovariectomized mice administered estradiol (P = 0.002).
LIMITATIONS, REASONS FOR CAUTION:
This study was performed in one only species.
WIDER IMPLICATIONS OF THE FINDINGS:
Results of this study demonstrate the uterine regulation of BDNF and NGFR by estradiol, and highlight the striking difference between hormone exposure during the estrous cycle and daily estradiol exposure after ovariectomy on neurotrophin expression in the uterus. The results also show the spatial regulation of NGFR in the uterus in response to ovarian hormones. Sustained estrogen exposure, as seen in estrogen-dependent disease, may alter the delicate neurotrophin balance and inappropriately activate potent BDNF-NTRK2 pathways which are capable of contributing to endometrial pathology.
STUDY FUNDING/COMPETING INTERESTS:
This study was supported by the Canadian Institutes of Health Research (CIHR) (W.G.F.), a NSERC Discovery Grant (W.G.F.), and a Vanier Canada Graduate Scholarship-CIHR (J.M.W.). J.M.W. is a member of the CIHR sponsored Reproduction and Early Development in Health training program. The authors declare no conflicts of interest.
Med J Islam Repub Iran. 2014 Oct 4;28:107.
Effect of Letrozole on endometriosis-related pelvic pain.
Almassinokiani F1, Almasi A2, Akbari P3, Saberifard M4.
To determine the role of Letrozole, an aromatase inhibitor, in the treatment of endometriotic pain.
In this prospective, randomized, controlled clinical trial in minimally invasive surgery research center, 51 women with pelvic endometriosis and endometriotic pain (dyspareunia, dysmenorrhea, pelvic pain) score of 5 or more (for at least one of these endometriotic pain), after laparoscopic diagnosis and conservative laparoscopic surgery were treated with either Letrozole plus OCP (n=25) or only OCP (n=26) for 4 months continuously.
Using VAS test, the score of dyspareunia, dysmenorrhea and pelvic pain 4 months after the laparoscopic surgery declined significantly in both groups but the difference between results of the two groups was not significant.
Both treatment modalities showed comparable effectiveness in the treatment of pains related to endometriosis and in comparison with OCP, Letrozole did not affect the outcome.
Arch Gynecol Obstet. 2015 Aug;292(2):377-81.
Expression of p27 and Jun activation domain-binding protein 1 in endometriosis.
Kim TH1, Lee HH, Chung SH, Park J, Lee A.
The goal of this study was to investigate differential expression of the cell cycle signaling proteins p27 and Jun activation domain-binding protein 1 (Jab1) in benign ovarian cysts of patients with endometriosiscompared to controls.
Ovarian tissues of 26 endometriosis and 28 non-endometriosis patients were used to evaluate expression of p27 and Jab1 by immunohistochemistry.
There are no differences in clinical characteristics between the endometriosis and non-endometriosisgroup. In the endometriosis group, CD10, Jab1 and p27 were positive in 50, 48.3 and 57.7 % of cases, respectively, compared to 14.3, 17.9 and 50 %, respectively, in the non-endometriosis group. Jab1 and p27 were positive in 69.2 and 84.6 %, respectively, of the definite endometriosis cases.
These results demonstrate that Jab1 expression was increased in endometriosis, while p27 expression was similar in the endometriosis and non-endometriosis groups.
Hum Reprod Update. 2015 May-Jun;21(3):340-52.
Gap junction connexins in female reproductive organs: implications for women’s reproductive health.
Connexins comprise a family of ~20 proteins that form intercellular membrane channels (gap junction channels) providing a direct route for metabolites and signalling molecules to pass between cells. This review provides a critical analysis of the evidence for essential roles of individual connexins in female reproductive function, highlighting implications for women’s reproductive health.
No systematic review has been carried out. Published literature from the past 35 years was surveyed for research related to connexin involvement in development and function of the female reproductive system. Because of the demonstrated utility of genetic manipulation for elucidating connexin functions in various organs, much of the cited information comes from research with genetically modified mice. In some cases, a distinction is drawn between connexin functions clearly related to the formation of gap junction channels and those possibly linked to non-channel roles.
RESULTS AND CONCLUSIONS:
Based on work with mice, several connexins are known to be required for female reproductive functions. Loss of connexin43 (CX43) causes an oocyte deficiency, and follicles lacking or expressing less CX43 in granulosa cells exhibit reduced growth, impairing fertility. CX43 is also expressed in human cumulus cells and, in the context of IVF, has been correlated with pregnancy outcome, suggesting that this connexin may be a determinant of oocyte and embryo quality in women. Loss of CX37, which exclusively connects oocytes with granulosa cells in the mouse, caused oocytes to cease growing without acquiring meiotic competence. Blocking of CX26 channels in the uterine epithelium disrupted implantation whereas loss or reduction of CX43 expression in the uterine stroma impaired decidualization and vascularization in mouse and human. Several connexins are important in placentation and, in the human, CX43 is a key regulator of the fusogenic pathway from the cytotrophoblast to the syncytiotrophoblast, ensuring placental growth. CX40, which characterizes the extravillous trophoblast (EVT), supports proliferation of the proximal EVTs while preventing them from differentiating into the invasive pathway. Furthermore, women with recurrent early pregnancy loss as well as those with endometriosis exhibit reduced levels of CX43 in their decidua. The antimalaria drug mefloquine, which blocks gap junction function, is responsible for increased risk of early pregnancy loss and stillbirth, probably due to inhibition of intercellular communication in the decidua or between trophoblast layers followed by an impairment of placental growth. Gap junctions also play a critical role in regulating uterine blood flow, contributing to the adaptive response to pregnancy. Given that reproductive impairment can result from connexin mutations in mice, it is advised that women suffering from somatic disease symptoms associated with connexin gene mutations be additionally tested for impacts on reproductive function. Better knowledge of these essential connexin functions in human female reproductive organs is important for safeguarding women’s reproductive health.
Reprod Sci. 2015 Sep;22(9):1088-97.
Possible Role of α1-Antitrypsin in Endometriosis-Like Grafts From a Mouse Model of Endometriosis.
Tamura K1, Takashima H2, Fumoto K2, Kajihara T3, Uchino S3, Ishihara O3, Yoshie M2, Kusama K4, Tachikawa E2.
Previous study indicated that bleeding into the peritoneum may accelerate inflammatory response in endometriosis-like grafts in mice. To identify changes in protein levels in the grafts from mice that underwent unilateral ovariectomy (uOVX), which causes bleeding from ovarian arteries and vein, the grafts were generated by injecting a suspension of human endometrial cells in BALB/c nude female mice, and protein profile changes were compared with non-uOVX control mice. The level of α1-antitrypsin (α1-AT) decreased in grafts from nude mice that underwent uOVX. The levels of phosphorylated Akt, mammalian target of rapamycin, S6K, regulatory factors for cell survival, and of phosphorylated nuclear factor κB, an inflammatory mediator, were higher in endometriosis-like grafts from the uOVX group than from the control. The grafts were mostly comprised of stromal cells. The bioactivity of α1-AT was assessed by investigating cytokine expression in protease-activated receptor (PAR) 1/2 agonists-stimulated stromal cells. The PARs promoted the expression of interleukin 8 (IL-8), but treatment with α1-AT blocked IL-8 expression dose dependently. Knocking down α1-AT expression increased the constitutive IL-6, IL-8, and cyclooxygenase 2 expression as well as PAR1 agonist-stimulated IL-6 expression. These findings support the notion that decreased α1-AT protein in the grafts constituted with human endometrial cells in mice may have exacerbated inflammation in endometriosis-like grafts, suggesting the possible involvement of α1-AT in the pathophysiology of endometriosis.
Minerva Ginecol. 2015 Apr;67(2):149-67.
Decreased ovarian reserve: any new hope?
Alborzi S1, Madadi G, Samsami A, Soheil P, Azizi M, Alborzi M, Bakhshaie P.
While diminished ovarian reserve (DOR) predicts decreased ovarian response to stimulation, it does not necessarily foretell about the fecundity cycle. According to Bologna’s criteria laid down by the European Society of Human Reproduction and Embryology, old age, abnormal ovarian reserve tests such as antral follicle count (AFC) and anti-mullerian hormone (AMH) as well as prior suboptimal response to stimulation are the main factors representing DOR. Unfavorable response to maximal stimulation on two previous occasions may also represent DOR. Among the ovarian reserve tests, AMH and AFC are the most predictive values for DOR. Factors which may give rise to DOR include environmental factors, autoimmune or metabolic disorders, infections, genetic abnormalities, and iatrogenic causes (such as smoking, chemotherapy, radiation and gynecologic surgeries). Besides, studies have proposed endometriosis as a key contributor to DOR and hence emphasized on its proper management to prevent additional damages leading to compromised fertility. In summary, DOR is found to be a clinical challenge in the practice of fertility care with controversial countermeasures to prevent or treat the condition. Nevertheless, some promising measure such as: oocyte, embryo and tissue cryopreservation, ovarian transplantation, dietary supplementation and the transfer of mitochondria have offered hopes towards ameliorating the burden of DOR. This review attempts to discuss DOR from different perspectives and summarize some existing hopes in clinical practice.
Chin Med J (Engl). 2015 Feb 20;128(4):427-32
Efficacy and safety investigation of Kuntai capsule for the add-back therapy of gonadotropin releasing hormone agonist administration to endometriosispatients: a randomized, double-blind, blank- and tibolone-controlled study.
Chen JM, Gao HY1, Ding Y, Yuan X, Wang Q, Li Q, Jiang GH.
As a Chinese Traditional Medicine product, Kuntai capsule could improve the peri-menopausal symptoms in postmenopausal women. But it is still not clear whether Kuntai capsule has a good effect on alleviating peri-menopausal symptoms induced by gonadotropin releasing hormone agonist (GnRH-a) treatment. The purpose of this study was to investigate the clinical effectiveness and safety of Kuntai capsule, on peri-menopausal symptoms in endometriosis (EMS) patients, with postoperative GnRH-a treatment.
Ninety EMS ovarian cyst women with postoperative GnRH-a administration were enrolled in the study, and were randomly divided into Kuntai group, Tibolone group, or blank Control group. The therapeutic strategy in Kuntai group was 4 Kuntai capsules tid,po for 12 weeks after the first GnRH-a injection, while Tibolone 2.5 mg qd, po for 12 weeks in Tibolone group. There was no drug addition in Control group. Climacteric complaints were evaluated by Kupperman menopausal index (KMI) and hot flash/sweating score. Liver and renal functions, lipid profile, serum sex hormone levels and endometrial thickness were measured, and the frequency of adverse events in Kuntai and Tibolone groups was recorded.
(1) Before GnRH-a therapy, the baseline parameter results were comparable in the three groups (P > 0.05). (2) After GnRH-a therapy, KMI and hot flash/sweating scores in all the three groups increased significantly (P < 0.05). At the 4 th week after GnRH-a therapy, KMI and hot flash/sweating score results were as follows: Control group > Kuntai group > Tibolone group (P < 0.05); at the 8 th and 12 th week after GnRH-a therapy, KMI and hot flash/sweating score in Control group were significantly higher than the other two groups (P < 0.05), and no significant difference was identified between Kuntai and Tibolone group (P > 0.05). (3) No statistical change took place in the liver and renal functions and lipid profile in all the three groups after the treatment (P > 0.05). (4) The posttherapeutic serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) level and endometrial thickness decreased significantly in all the three groups (P < 0.05). After therapy, serum E2 level in Tibolone group was obviously higher than the other two groups (P < 0.05), while FSH and LH levels were obviously lower (P < 0.05). (5) The incidence of vaginal bleeding, breast distending pain in Tibolne group was obviously higher than Kuntai group (P < 0. 05).
Kuntai capsule is effective on the peri-menopausal symptoms induced by postoperative GnRH-a administration to EMS patients, although its clinical effect might be a few weeks later than Tibolone. Kuntai capsule might be a little safer than Tibolone tablet.
Chin Med J (Engl). 2015 Feb 20;128(4):455-8.
Obstetric outcomes in Chinese women with endometriosis: a retrospective cohort study.
Lin H, Leng JH1, Liu JT, Lang JH.
The effect of endometriosis on obstetric outcomes is still ambiguous. The aim of our study was to determine the association between endometriosis and adverse obstetric outcomes in a cohort of Chinese women.
A retrospective cohort study was undertaken to compare obstetric outcomes between 249 women with endometriosis and 249 women without endometriosis. All women were nulliparous and achieved singleton pregnancies naturally. Women with endometriosis were diagnosed during surgery and confirmed histologically. Odds ratios (ORs) and 95% confidence intervals (CIs) of measures of obstetric outcomes were calculated.
Women with endometriosis showed significantly increased risks of preterm labor (adjusted OR, 2.42; 95% CI, 1.05-5.57), placenta previa (adjusted OR, 4.51; 95% CI, 1.23-16.50), and cesarean section (adjusted OR, 1.93; 95% CI, 1.31-2.84). No significant differences were observed in the incidence of pregnancy-induced hypertension, fetal growth restriction, small for gestational age, placental abruption, or luteal support in the first trimester between the two groups.
Women with endometriosis are at a higher risk of preterm labor, placenta previa, and cesarean section during pregnancy and need additional care.
Chin Med J (Engl). 2015 Feb 20;128(4):520-7
Identification of biomarkers for endometriosis using clinical proteomics.
Zhao Y, Liu YN, Li Y, Tian L, Ye X, Cui H, Chang XH1.
We investigated possible biomarkers for endometriosis (EM) using the ClinProt technique and proteomics methods.
We enrolled 50 patients with EM, 34 with benign ovarian neoplasms and 40 healthy volunteers in this study. Serum proteomic spectra were generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MS) combined with weak cationic exchange (WCX) magnetic beads. Possible biomarkers were analyzed by a random and repeat pattern model-validation method that we designed, and ClinProtools software, results were refined using online liquid chromatography-tandem MS.
We found a cluster of 5 peptides (4210, 5264, 2660, 5635, and 5904 Da), using 3 peptides (4210, 5904, 2660 Da) to discriminate EM patients from healthy volunteers, with 96.67% sensitivity and 100% specificity. We selected 4210 and 5904 m/z, which differed most between patients with EM and controls, and identified them as fragments of ATP1B4, and the fibrinogen alpha (FGA) isoform 1/2 of the FGA chain precursor, respectively.
ClinProt can identify EM biomarkers, which – most notably – distinguish even early-stage or minimal disease. We found 5 stable peaks at 4210, 5264, 2660, 5635, and 5904 Da as potential EM biomarkers, the strongest of which were associated with ATP1B4 (4210 Da) and FGA (5904 Da); this indicates that ATP1B4 and FGA are associated with EM pathogenesis.
Indian J Med Res. 2014 Nov;140 Suppl:S78-81
Association of western diet & lifestyle with decreased fertility.
It has been accepted that food customs are closely associated with the quality of life in both men and women’s reproductive life. Food customs are speculated to not only influence the present lifestyle but also to induce gynaecological disorders such as dysmenorrhoea, spermatogenesis and irregular menstruation. though there is no consistent definition of regular or normal menstruation, epidemiologic evaluation of menstrual cycle has been becoming an important issue. In addition, latent development of organic diseases such as endometriosis, which are accompanied by dysmenorrhoea, is a concern under the current nutritional environment. Thus, it is an important issue to evaluate the present situation of eating habits in couples and estimate the influence of these habits on the quality of reproductive functions. A multi-faceted therapeutic approach to improving fertility involves identifying harmful environmental and occupational risk factors, while correcting underlying nutritional imbalances to encourage optimal reproduction and its function.
Int J Clin Exp Pathol. 2014 Dec 1;7(12):8996-9001.
Ovarian malignant mixed germ cell tumor with clear cell carcinoma in a postmenopausal woman.
Yu XJ1, Zhang L1, Liu ZP2, Shi YQ1, Liu YX1.
Malignant germ cell tumors of the ovary are very rare and account for about 2-5% of all ovarian tumors of germ origin. Most patients are adolescent and young women, approximately two-thirds of them are under 20 years of age, occasionally in postmenopausal women. But clear cell carcinoma usually occurs in older patients (median age: 57-year old), and closely related with endometriosis. Here we report a case of a 55-year old woman with right ovarian mass that discovered by B ultrasonic. Her serum levels of human chorionic gonadotropin (hCG) and α-fetoprotein (AFP) were elevated. Pathological examination revealed the tumor to be a mixed germ cell tumor (yolk sac tumor, embryonal carcinoma and mature teratoma) with clear cell carcinoma in a background of endometriosis. Immunohistochemical staining showed SALL4 and PLAP were positive in germ cell tumor area, hCG, CD30 and OCT4 were positive in epithelial-like cells and giant synctiotrophoblastic cells, AFP, AAT, CD117 and Glyp3 were positive in yolk sac component, EMA and CK7 were positive in clear cell carcinoma, CD10 was positive in endometrial cells of endometriotic area. She was treated with surgery followed by seven courses of chemotherapy. She is well and serum levels of hCG and AFP have been decreased to normal levels.
Clin Endosc. 2015 Jan;48(1):74-7.
An extremely rare case of gastric subepithelial tumor: gastric endometriosis.
Ha JK1, Choi CW1, Kim HW1, Kang DH1, Park SB1, Kim SJ1, Hong JB1.
Endometriosis is a disease characterized by the presence of endometrial tissue outside of the uterine cavity. It is common in women of childbearing age, and is most frequently located in the pelvic cavity. Approximately 10% of endometriosis cases occur outside of the pelvic cavity in locations such as the intestines, genitourinary system, kidneys, lungs, and skin. However, there have been few reports of endometriosis in the stomach. Here, we report a rare case of endometriosis that presented as a subepithelial stomach tumor.
Reprod Sci. 2015 Jul;22(7):873-83.
Dating Endometriotic Ovarian Cysts Based on the Content of Cyst Fluid and its Potential Clinical Implications.
Guo SW1, Ding D2, Shen M2, Liu X3.
This study was undertaken to test the hypotheses that, due to gradual accumulation of dead erythrocytes and their ingested products resulting from repeated hemorrhage, older endometriomas (whitish in color) contain chocolate fluid with higher iron content than younger (brownish/blackish in color) ones with concomitant higher collagen content and more adhesions. We recruited 30 premenopausal women with histologically confirmed ovarian endometriomas and collected samples of their endometriotic lesions and chocolate fluid and measured the viscosity, density, and the concentration of total bilirubin, ferritin, and free iron of the chocolate fluid. We also evaluated the lesion color and adhesion scores. In addition, we performed Masson trichrome and Picro-Sirius red staining on all endometriotic cysts and evaluated the extent of fibrosis in the lesions. We found that fluids taken from white-colored endometriomas had significantly higher concentration of total bilirubin, ferritin, and free iron, respectively, than black/brown-colored ones. In addition, older cysts had fluids that had significantly higher density and viscosity. Fluid density correlated positively with the concentrations of total bilirubin, ferritin, and free iron. Older lesions had significantly more collagen content and higher adhesion scores. Taken together, these data supports the notion that older cysts, having experienced more bleeding episodes, contain chocolate fluid that is higher in viscosity, density, and iron content and higher fibrotic content than younger ones. This provides another piece of evidence that endometriotic lesions are wounds that undergo repeated injury and repair, resulting ultimately fibrotic lesions that are resistant to hormonal treatment.
Hum Reprod. 2015 Apr;30(4):987-93.
Replication and meta-analysis of previous genome-wide association studies confirm vezatin as the locus with the strongest evidence for association with endometriosis.
Pagliardini L1, Gentilini D2, Sanchez AM1, Candiani M1, Viganò P3, Di Blasio AM2.
Is it possible to replicate the genetic association of single nucleotide polymorphisms (SNPs) rs13394619, rs4141819, rs7739264, rs17694933 and rs10859871 in five genetic loci previously identified as associated with endometriosis in an Italian Caucasian population?
SNP rs10859871 near the vezatin (VEZT) gene was found to be significantly associated with endometriosis in general while SNPs rs17694933 and rs4141819 were associated with Stage III/IV and ovarian disease, respectively.
WHAT IS KNOWN ALREADY:
Endometriosis represents a complex disease in which the phenotypic manifestations are influenced by both genetic and environmental factors. Recent genome-wide association studies (GWASs) have allowed to identify some SNPs associated with the predisposition to the disease. A meta-analysis published in 2014 combined results from GWAS and replication studies showing that of the nine loci found to be associated with the disease in at least one of the studies, six (rs7521902, rs1270667, rs13394619, rs7739264, rs1537377 and rs10859871) remained genome-wide significant while two others (rs1250248 and rs4141819) showed borderline genome-wide significant association with more severe disease.
STUDY DESIGN, SIZE, DURATION:
Allele frequencies of selected SNPs (rs13394619, rs4141819, rs7739264, rs17694933 and rs10859871) were investigated in 305 women with laparoscopically proven endometriosis, 285 laparoscopic controls and 2425 healthy, blood donor controls from the general population. A meta-analysis with previous data was also conducted.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
A total of 590 women who underwent endoscopic surgery were enrolled in the study and a blood sample was collected. After DNA extraction, genotype was obtained using Taq-Man pre-designed assay. Genotype data from healthy blood donor women were obtained from an existing genotype bank.
MAIN RESULTS AND THE ROLE OF CHANCE:
A statistically significant association with endometriosis was found for SNP rs10859871, close to the VEZT gene, compared with both general population [odds ratio (OR) = 1.43, 95% confidence interval (CI): 1.20-1.71, P = 6.9 × 10(-5)] and laparoscopic controls (OR = 1.58, 95% CI: 1.24-2.02, P = 2.1 × 10(-4)). Meta-analysis with previous data confirmed the rs10859871 SNP as that with the strongest evidence for association with endometriosis (OR = 1.19, 95% CI: 1.15-1.24, P = 7.9 × 10(-20)). A further meta-analysis conducted using data from Stage III-IV endometriosis resulted in stronger genome-wide significant effect sizes for four out of the five SNPs tested.
LIMITATIONS, REASONS FOR CAUTION:
The inability to confirm all previous demonstrated associations considering all stages of endometriosis may be due to a lack of statistical power and differences in the definition of cases included.
WIDER IMPLICATIONS OF THE FINDINGS:
The associations with the SNPs identified so far have been obtained with a relatively small sample size supporting a limited heterogeneity across the various datasets. This represents an important advance in the identification of genetic markers of this disease.
STUDY FINDING/COMPETING INTERESTS:
No funding to declare. The authors have no competing financial interests in relation to the content of this research paper.
Int J Womens Health. 2015 Feb 3;7:161-9.
Anti-inflammatory, antiangiogenic, and apoptosis-inducing activity of DLBS1442, a bioactive fraction of Phaleria macrocarpa, in a RL95-2 cell line as a molecular model of endometriosis.
Tandrasasmita OM1, Sutanto AM1, Arifin PF1, Tjandrawinata RR1.
DLBS1442 is a bioactive fraction extracted from the fruit of the native Indonesian plant, Phaleria macrocarpa (Scheff.) Boerl (Thymelaceae). This bioactive fraction is a potential treatment for dysmenorrhea and endometriosis. The present study investigated the pharmacological action of DLBS1442 in endometrial cells. The effect of various doses of DLBS1442 (0-200 μg/mL) over 24 hours was studied using the human endometrial RL95-2 cell line to observe its effect on angiogenesis, cell migration, estrogen and progesterone receptor levels, the eicosanoid pathway, cell viability, and apoptosis. The impact of DLBS1442 on nuclear factor kappa B (NFκB) and the eicosanoid pathway was also studied through its marker gene expression using a quantitative real-time polymerase chain reaction method. DLBS1442 showed an ability to inhibit angiogenesis and cell migration in a dose-dependent manner. At a dose of 100 μg/mL, DLBS1442 increased the cell population in sub-G1 phase from 7% to 34%. DLBS1442 also significantly downregulated the estrogen receptor level and upregulated the progesterone receptor level. Further, it inhibited the eicosanoid signaling pathway by reducing the NFκB transcription level and subsequent reduction of inducible nitric oxide synthase. A dose-dependent decrease in viability and increased apoptosis in RL95-2 cells were also evident after exposure to DLBS1442, where the IC50 was obtained at around 100 μg/mL. In conclusion, DLBS1442 is a potential agent for alleviating symptoms of endometriosis via its antiangiogenic, anti-inflammatory, and proapoptotic activity.
PLoS One. 2015 Feb 13;10(2):
Low birth weight is strongly associated with the risk of deep infiltrating endometriosis: results of a 743 case-control study.
Borghese B1, Sibiude J2, Santulli P3, Lafay Pillet MC2, Marcellin L1, Brosens I4, Chapron C1.
The influence of intrauterine environment on the risk of endometriosis is still controversial. Whether birth weight modifies the risk of endometriosis in adulthood remains an open question. For this purpose, we designed a case-control study involving 743 women operated on for benign gynecological indications from January 2004 to December 2011. Study group included 368 patients with histologically proven endometriosis: 54 superficial endometriosis (SUP), 79 endometriomas (OMA) and 235 deep infiltrating endometriosis (DIE). Control group included 375 patients without endometriosis as surgically checked. Mean birth weights were compared between patients and controls, according to endometriosis groups and rAFS stages. Mean birth weight was significantly lower for patients with endometriosis as compared to controls (3,119 g ± 614 and 3,251 g ± 557 respectively; p = 0.002). When compared to controls, patients with DIE had the lowest birth weight with a highly significant difference (3,103 g ± 620, p = 0.002). In univariate analysis, patients with low birth weight (LBW), defined as a BW < 2,500 g, had a higher risk of endometriosis, especially DIE, as compared to the reference group (OR = 1.5, 95%CI: 1.0-2.3 and OR = 1.7, 95%CI: 1.0-2.7, respectively). Multivariate analysis, adjusted on ethnicity and smoking status, showed the persistence of a significant association between endometriosis and LBW with a slight increase in the magnitude of the association (aOR = 1.7, 95%CI: 1.0-2.6 for endometriosis, aOR = 1.8; 95%CI: 1.1-2.9 for DIE). In conclusion, LBW is independently associated with the risk of endometriosis in our population. Among patients with LBW, the risk is almost two-times higher to develop DIE. This association could reflect common signaling pathways between endometriosis and fetal growth regulation. There is also the possibility of a role played by placental insufficiency on the development of the neonate’s pelvis and the occurrence of neonatal uterine bleeding that could have consequences on the risk of severe endometriosis.
Regul Toxicol Pharmacol. 2015 Apr;71(3):371-8
A critical examination of the mode of action of quinacrine in the reproductive tract in a 2-year rat cancer bioassay and its implications for human clinical use.
Haseman JK1, Growe RG2, Zeiger E3, McConnell EE4, Luster MI5, Lippes J6.
A rat carcinogenicity bioassay (CaBio) of quinacrine was reanalyzed to investigate its mode of tumor induction. Quinacrine’s effects in the rat uterus when administered as a slurry in methylcellulose were contrasted with the human clinical experience which uses a solid form of the drug, to determine the relevance of the tumors produced in the rat to safe clinical use of quinacrine for permanent contraception (QS). A review was performed of the study report, dose feasibility studies, and clinical evaluations of women who had undergone the QS procedure. The top three doses of quinacrine in the CaBio exceeded the maximum tolerated dose, and produced chronic damage, including inflammation, resulting in reproductive tract tumors. Chronic inflammation was significantly correlated with the tumors; there was no evidence of treatment-related tumors in animals without chronic inflammation or other reproductive system toxicity. Because such permanent uterine damage and chronic toxicity have not been observed in humans under therapeutic conditions, we conclude that this mode of action for tumor production will not occur at clinically relevant doses in women who choose quinacrine for permanent contraception.
Ann Surg Oncol. 2015 Aug;22(8):2738-45.
Effect of Endometriosis on the Prognosis of Ovarian Clear Cell Carcinoma: A Two-Center Cohort Study and Meta-analysis.
Kim HS1, Kim MA, Lee M, Suh DH, Kim K, No JH, Chung HH, Kim YB, Song YS.
Whether endometriosis affects the prognosis of ovarian clear cell carcinoma (OCCC) remains controversial despite the relationship between OCCC and endometriosis. A two-center cohort study and meta-analysis were performed to investigate the effect of endometriosis on the prognosis of OCCC.
The study reviewed the clinicopathologic data of 109 patients with OCCC arising (n = 47) or not arising (n = 62) in endometriosis between 1997 and 2012 at two tertiary medical centers. Tumor response and survival were compared between the two groups. For further evaluation, PubMed, EmBase, and the Cochrane Library were searched, and a meta-analysis was conducted using 10 cohort studies published from March 1996 to May 2014, including the current cohort study.
Complete response did not differ between the patients with OCCC arising in endometriosis and those without endometriosis (77.5 vs. 87.3 %; P = 0.444). Early-stage disease and optimal debulking surgery were the only independent factors that reduced the risk of noncomplete response (adjusted odds ratios 0.203 and 0.038; 95 % confidence intervals [CIs] 0.045-0.920 and 0.006-0.226, respectively). Progression-free survival (PFS) and overall survival (OS) did not differ between the two groups. Early-stage disease and optimal debulking surgery were the only favorable factors that improved PFS (adjusted hazard ratios [HRs] 0.216 and 0.332; 95 % CIs 0.099-0.469 and 0.150-0.732, respectively) and OS (adjusted HRs 0.099 and 0.339; 95 % CIs 0.039-0.252 and 0.141-0.815, respectively). Furthermore, crude and subgroup meta-analyses showed no effect of endometriosison PFS or OS in OCCC patients.
J Minim Invasive Gynecol. 2015 May-Jun;22(4):684-6.
Periclitoral endometriosis: the dilemma of a chronic disease invading a rare location.
Grimstad FW1, Carey E2.
Endometriosis affects 6% to 10% of women of reproductive age; extrapelvic endometriosis is considered a rare event with perineal endometriosis being even rarer still (only a few cases of spontaneous episodes described, the majority being from episiotomy scars). We present a unique case of periclitoral endometriosis, which to the best of our knowledge is the first in the literature. It is a 29-year-old nulligravida female with a painful fluctuant right periclitoral mass that had been growing with no response to antibiotic therapy. At the initial removal, pathology reported the lesion as endometriosis. The patient was placed on oral contraceptives, and she was noted to have monthly swelling and shrinking of the site with her menstrual cycles. When she went off hormonal contraception, she represented with the growing lesion 3.5 weeks after her last menses; she underwent re-excision. Because of the extension of the lesion medially and its adherence to the clitoral body, the decision was made to evacuate only as much of the capsule that could be safely identified to minimize the risk of damaging the clitoris. Complete excision in this case was difficult without sacrificing a portion of the clitoris and potentially resulting in decreased sexual function and persistent clitoral pain. In a patient in whom complete excision is not possible, there is potential for mass recurrence in the setting of residual tissue. Reviewing the literature suggests that there are risks with both recurrence and clitoral excision. We found that in-depth patient counseling, hormonal suppression, and close follow-up are necessary when dealing with periclitoral endometriosis postexcision.
Obstet Gynecol Clin North Am. 2015 Mar;42(1):87-101
Current strategies for endometriosis management.
Endometriosis is a common gynecologic disorder that persists throughout the reproductive years. Although endometriosis is a surgical diagnosis, medical management with ovarian suppression remains the mainstay of long-term management with superimposed surgical intervention when needed. The goal of surgery should be excision or ablation of all visible disease to minimize risk of recurrence and need for repeat surgeries. When infertility is the presenting symptom, surgical therapy in addition to assisted reproductive technology can improve chances of conception; however, the treatment approach depends on stage of disease and other patient characteristics that affect fecundity.
Fertil Steril. 2015 Apr;103(4):1049-52.
Altered uterine contractility in women with chronic endometritis.
Pinto V1, Matteo M2, Tinelli R3, Mitola PC1, De Ziegler D4, Cicinelli E5.
To evaluate the alterations in endometrial waves (EW) originating from the contraction of the subendometrial myometrial layer in the periovulatory and midluteal phases in women diagnosed with chronic endometritis (CE).
Forty-five women referred for hysteroscopy and diagnosed with CE.
Three-minute recording of transvaginal ultrasound scanning on sagittal uterine plane at periovulatory (cycle days 11-14) and midluteal phase (cycle days 19-22).
MAIN OUTCOME MEASURE(S):
Direction and frequency of EW measured by transvaginal ultrasound scan.
The direction and frequency of EW were analyzed offline as accelerated (four to eight times normal speed) image sequences using video editing software, and the results were compared with 45 cycling women without CE. The EW pattern was significantly different when comparing the women with CE and controls at both the periovulatory and midluteal phases. During the periovulatory phase, we observed retrograde contractions in 26.7% versus 88%, anterograde in 24% versus 0, opposing in 22.7% versus 12%, not propagated in 13.3% versus 0, and absent in 13.3% versus 0, respectively, in the CE cases versus the control group. During the midluteal phase, we observed not propagated (41.3% vs. 61.3%), opposing (24% vs. 25.4%), absent (16.1% vs. 13.3%), anterograde (13.3% vs. 0), and retrograde (5.3% vs. 0), respectively, in the CE cases versus the control group.
Women with CE show altered EW patterns in both the periovulatory and midluteal phases. Altered uterine contractility may aid in explaining the symptoms related to CE such as pain, abnormal uterine bleeding, infertility, and possibly endometriosis.
Fertil Steril. 2015 May;103(5):1236-43.
Second surgery for recurrent unilateral endometriomas and impact on ovarian reserve: a case-control study.
Ferrero S1, Scala C2, Racca A2, Calanni L2, Remorgida V2, Venturini PL2, Leone Roberti Maggiore U2.
To investigate the impact on ovarian reserve of second laparoscopic surgery for recurrent unilateral endometriomas.
University teaching hospital.
This study included patients who underwent stripping of endometriomas (diameter ≥4 cm) and were followed-up at our institution. Case subjects had second surgery for recurrent unilateral endometriomas (n = 18); control subjects had no recurrence and no second surgery (n = 18).
This case-control study was based on a retrospective analysis of a prospectively collected database including patients who underwent surgery for endometriomas at our institution.
MAIN OUTCOME MEASURE(S):
The primary outcome of the study was to assess the changes in antimüllerian hormone (AMH) levels in each study group and between the two study groups. The secondary outcomes of the study were to assess the changes in basal FSH, antral follicle count (AFC), and ovarian volume in each study group and between the two study groups.
In both study groups, primary surgery decreased AMH, increased basal FSH, and decreased the AFC of the operated ovary. Before second surgery, case subjects had AMH, basal FSH, and AFC similar to control subjects. After second surgery, case subjects had lower AMH, higher basal FSH, and lower AFC of the affected ovary than before surgery; the volume of the operated ovary was lower than that of the contralateral ovary.
The laparoscopic stripping of recurrent ovarian endometriomas is associated with a high risk of ovarian reserve damage and ovarian failure.
Fertil Steril. 2015 Apr;103(4):990-1000.
P-selectin as a potential therapeutic target for endometriosis.
Guo SW1, Ding D2, Geng JG3, Wang L4, Liu X5.
To test the hypothesis that P-selectin plays a critical role in the development of endometriosis and that targeting P-selectin has therapeutic potential.
Prospective, randomized study.
The first experiment used 24 each of female adult P-selectin knockout mice and C57BL/6 wild-type mice, and 96 male green fluorescent protein (GFP) transgenic mice. The second experiment used 16 female adult C57BL/6 mice.
In experiment 1, P-selectin knockout and wild-type mice alternately served as donors and recipients for the transplantation of endometrial tissue fragments into the peritoneal cavity to induce endometriosis. Two weeks later all four groups were each randomly divided into two equal-sized subgroups, receiving either green fluorescent protein-expressing platelets or saline infusion. In experiment 2, 2 weeks after the surgical induction of endometriosis, the mice were randomly divided into two groups, one receiving a 2-week treatment with a recombinant P-selectin protein and the other, non-immune IgG, both by intraperitoneal injection.
MAIN OUTCOME MEASURE(S):
Lesion size, hotplate latency, and immunohistochemistry analysis of platelet aggregation, angiogenesis, transforming growth factor β1, α-smooth muscle actin, collagen I, and the extent of macrophage infiltration in ectopic implants. The extent of fibrosis also was evaluated in experiment 2.
P-selectin deficiency significantly retarded the development of endometriosis in a mouse model of endometriosis. In addition, soluble P-selectin treatment markedly reduced the lesion size in mouse through decreased platelet aggregation and angiogenesis, improved general hyperalgesia, and reduced the extent of macrophages infiltration, resulting in reduced fibrotic tissue content.
Targeting P-selectin-mediated platelet adhesion onto endometriotic lesions holds promise as a novel therapeutics for treating endometriosis.
Abdom Imaging. 2015 Oct;40(7):2512-6.
Susceptibility-weighted MRI of extra-ovarian endometriosis: preliminary results.
Takeuchi M1, Matsuzaki K2, Harada M2.
Extra-ovarian endometriosis (EOE) usually appears as solid masses mimicking neoplasms both clinically and radiologically. Detection of blood products within a lesion may be suggestive of its endometriotic nature. We present a descriptive study of MR imaging findings that include susceptibility-weighted imaging (SWI) for patients with EOE.
Eight pathologically proven EOE (3 bowel, 2 bladder and 3 abdominal wall) were evaluated. Fat-saturated T1-weighted images (fsT1WI) and SWI were obtained using 1.5T MR imaging. Images were reviewed for the presence of signal voids on SWI and of high-intensity foci on fsT1WI.
High-intensity foci reflecting subacute hemorrhage were detected in 4 of 8 lesions (50%) on fsT1WI, whereas signal voids reflecting acute to chronic hemorrhage were detected in all 8 lesions (100%) on SWI.
SWI is a sensitive MRI technique which demonstrates hemorrhage of varying chronicity in patients with EOE and may improve future MRI characterization of EOE.
Reprod Biomed Online. 2015 Apr;30(4):415-20.
Analysis of WNT4 polymorphism in Chinese Han women with endometriosis.
Wu Z1, Yuan M1, Li Y1, Fu F1, Ma W1, Li H1, Wang W2, Wang S3.
Endometriosis is a complex disease that is influenced by genetic and environmental factors. In endometriosis, WNT4 plays a likely role owing to its biological functions. In this study, the TaqMan allelic discrimination technique was used to investigate the relationship between endometriosis and four single nucleotide polymorphisms in WNT4 (rs7521902 [A/C], rs16826658 [G/T], rs7515106 [C/T] and rs2235529 [A/G]) in Chinese Han women. A total of 646 patients with endometriosis and 766 normal controls were recurited. Regression analyses revealed that rs2235529 was a risk locus for endometriosis (P = 1.80E-03, OR, 95% CI = 1.311, 1.129 to 1.522), particularly in patients with stage III and IV disease. No significant association was found between endometriosisand rs7521902 (A/C), rs16826658 (G/T), or rs7515106 (C/T). For each of the four single nucleotide polymorphisms, no association was found between patients with endometriosis-related infertility or primary infertility and the controls. The results demonstrated that WNT4 rs2235529 is associated with endometriosis in Chinese Han women, which may result in aberrant expression of WNT4, leading to the pathogenesis of endometriosis.
Acta Gastroenterol Belg. 2014 Dec;77(4):433-4.
Colonic obstruction in a 45 year old female.
De Weerdt V, Bossuyt P, Peperstraete L.
We present a case of an unusual cause of colonic obstruction in a 45 year old female. The woman presented at the emergency department with a large bowel obstruction. Computed tomography of the abdomen showed distension of the colon with a lesion in the sigmoid colon with suspicion of a colonic malignancy. She underwent an urgent Hartmann procedure. Histology of the resection specimen revealed endometriosis. This patient did not have any symptoms suggestive of endometriosis. When a woman of childbearing age presents with large bowel obstruction, endometriosis should be considered in the differential diagnosis. This patient had a hysterectomy with bilateral salpingo-oophorectomy, what maked the diagnosis of endometriosis less evident.
Int J Surg Oncol. 2015;2015:790235.
Clear cell adenocarcinoma of the urethra: review of the literature.
Clear cell adenocarcinoma of the urethra (CCAU) is extremely rare and a number of clinicians may be unfamiliar with its diagnosis and biological behaviour.
To review the literature on CCAU.
Various internet databases were used.
(i) CCAU occurs in adults and in women in the great majority of cases. (ii) It has a particular association with urethral diverticulum, which has been present in 56% of the patients; is indistinguishable from clear cell adenocarcinoma of the female genital tract but is not associated with endometriosis; and probably does not arise by malignant transformation of nephrogenic adenoma. (iii) It is usually, readily distinguished from nephrogenic adenoma because of greater cytological a-typicality and mitotic activity and does not stain for prostate-specific antigen or prostatic acid phosphatase. (iv) It has been treated by anterior exenteration in women and cystoprostatectomy in men and at times by radiotherapy; chemotherapy has rarely been given. (v) CCAU is aggressive with low 5-year survival rates. (vi) There is no consensus opinion of treatment options that would improve the prognosis.
Few cases of CCAU have been reported. Urologists, gynaecologists, pathologists, and oncologists should report cases of CCAU they encounter and enter them into a multicentric trial to determine the best treatment options that would improve the prognosis.
Hum Mol Genet. 2015 Jun 1;24(11):3092-103.
Role of Foxl2 in uterine maturation and function.
Bellessort B1, Bachelot A1, Heude É1, Alfama G1, Fontaine A1, Le Cardinal M1, Treier M2, Levi G3.
Foxl2 codes for a forkhead/HNF3 transcription factor essential for follicular maturation and maintenance of ovarian identity. FOXL2 mutations are associated with Blepharophimosis, Ptosis and Epicanthus inversus Syndrome (BPES) characterized by eyelid malformations (types I and II) and premature ovarian insufficiency (type I). We show that Foxl2 is not only expressed by the ovary, but also by other components of the mouse female reproductive tract, including the uterus, the cervix and the oviduct. In the uterus, Foxl2 expression is first observed in the neonatal mesenchyme and, during uterine maturation, persists in the stroma and in the deep inner myometrial layer (IML). In the adult, Foxl2 is expressed in the differentiated stromal layer, but no longer in the myometrium. Conditional deletion of Foxl2 in the postnatal (PN) uterus using Progesterone Receptor-cre (Pgr(cre/+)) mice results in infertility. During PN uterine maturation Pgr(cre/+); Foxl2(flox/flox) mice present a severely reduced thickness of the stroma layer and an hypertrophic, disorganized IML. In adult Pgr(cre/+); Foxl2(flox/flox) mice a supplementary muscular layer is present at the stroma/myometrium border and vascular smooth muscle cells fail to form a coherent layer around uterine arteries. Wnt signalling pathways play a central role in uterine maturation; in Pgr(cre/+); Foxl2(flox/flox) mice, Wnt genes are deregulated suggesting that Foxl2 acts through these signals. In humans, thickening of the IML (also called “junctional zone”) is associated with reduced fertility, endometriosis and adenomyosis. Our data suggest that Foxl2 has a crucial role in PN uterine maturation and could help to understand sub-fertility predisposition in women.
Minerva Ginecol. 2015 Apr;67(2):195-205.
Surgery for endometriomas before IVF: what are the benefits and risks?
Endometriosis is present in up to one-third of infertility patients. In a subset of these patients, work-up will reveal the presence of an endometrioma. When the endometrioma is causing pelvic pain or dysmenorrhea, removal can greatly improve pain and quality of life. However, in the patient preparing for an in-vitro fertilization (IVF) cycle removal of an endometrioma can delay treatment. It is critical to know the benefits and risk of such a procedure prior to proceeding with surgical endometrioma removal. A great deal of literature had been published on the effect of endometriomas on fertility and IVF outcomes. In this review, we will summarize the current literature addressing the effects of endometrioma removal on ovarian response and pregnancy rates following IVF.
Altern Ther Health Med. 2015 Feb 17.
Ten-year Retrospective Study on the Efficacy of a Manual Physical Therapy to Treat Female Infertility.
Rice AD, Patterson K, Wakefield LB, Reed ED, Breder KP, Wurn BF, King Iii R, Wurn LJ.
Background • Female infertility is a complex issue encompassing a wide variety of diagnoses, many of which are caused or affected by adhesions. Objectives • The study intended to examine the rates of successful treatment of infertile women using a protocol of manual physical therapy to address underlying adhesive disease leading to infertility. Methods • The research team designed a retrospective chart review. Setting • The study took place in a private physical therapy clinic. Participants • Participants were 1392 female patients who were treated at the clinic between the years of 2002 and 2011. They had varying diagnoses of infertility, including occluded fallopian tubes, hormonal dysfunction, and endometriosis, and some women were undergoing in vitro fertilization (IVF). Intervention • All patients underwent whole-body, patient-centered treatments that used a protocol of manual physical therapy, which focused on restoring mobility and motility to structures affecting reproductive function. Outcome Measures • Improvements demonstrated in the condition(s) causing infertility were measured by improvements in tubal patency and/or improved hormone levels or by pregnancy. Results • The results included a 60.85% rate of clearing occluded fallopian tubes, with a 56.64% rate of pregnancy in those patients. Patients with endometriosis experienced a 42.81% pregnancy rate. The success rate was 49.18% for lowering elevated levels of follicle stimulating hormone (FSH), with a 39.34% pregnancy rate in that group, and 53.57% of the women with polycystic ovarian syndrome (PCOS) achieved pregnancy. The reported pregnancy rate for patients who underwent IVF after the therapy was 56.16%. The results also suggested that the treatment was effective for patients with premature ovarian failure (POF). Conclusion • The manual physical therapy represented an effective, conservative treatment for women diagnosed as infertile due to mechanical causes, independent of the specific etiology.
Evid Based Complement Alternat Med. 2015;
Effect of GuiXiong Xiaoyi Wan in Treatment of Endometriosis on Rats.
Objective. To evaluate the effect of GuiXiong Xiaoyi Wan (GXXYW) on the development of endometriosis in a rat model. Methods. Sprague-Dawley rats with surgically induced endometriosis were randomly treated with low-dose GXXYW, high-dose GXXYW, or vehicle (negative control) for 28 days. Immunohistochemistry was used to assess cell proliferation in the lesions. The terminal deoxynucleotidyl transferase- (TdT-) mediated dUTP biotin nick end labelling (TUNEL) method was performed to analyse the apoptosis induced by GuiXiong Xiaoyi Wan. The percentages of CD3+ lymphocytes, CD4+ lymphocytes, and CD8+ lymphocytes in the spleens of the rats were evaluated using flow cytometric analysis. Results. Treatment with GXXYW significantly decreased the lesion size, inhibited cell proliferation, and induced apoptosis in endometriotic tissue. The spleens of GXXYW-treated rats also demonstrated a significant increase in the percentage of CD4+ lymphocytes and a significant decrease in the percentage of CD8+ lymphocytes. Conclusions. These results suggest that, in a rat model, GXXYW may be effective in the suppression of the growth of endometriosis, possibly through the inhibition of cell proliferation, the induction of apoptosis of endometriotic cells, and the regulation of the immune system.
J Pathol. 2015 Jun;236(2):201-9.
Multifocal endometriotic lesions associated with cancer are clonal and carry a high mutation burden.
Anglesio MS1, Bashashati A2, Wang YK2, Senz J1, Ha G2, Yang W2, Aniba MR2, Prentice LM2, Farahani H2, Li Chang H1, Karnezis AN1, Marra MA3, Yong PJ4, Hirst M3,5, Gilks B1,6, Shah SP1,2, Huntsman DG1,2,4.
Endometriosis is a significant risk factor for clear cell and endometrioid ovarian cancers and is often found contiguous with these cancers. Using whole-genome shotgun sequencing of seven clear cell ovarian carcinomas (CCC) and targeted sequencing in synchronous endometriosis, we have investigated how this carcinoma may evolve from endometriosis. In every case we observed multiple tumour-associated somatic mutations in at least one concurrent endometriotic lesion. ARID1A and PIK3CA mutations appeared consistently in concurrent endometriosis when present in the primary CCC. In several cases, one or more endometriotic lesions carried the near-complete complement of somatic mutations present in the index CCC tumour. Ancestral mutations were detected in both tumour-adjacent and -distant endometriotic lesions, regardless of any cytological atypia. These findings provide objective evidence that multifocal benign endometriotic lesions are clonally related and that CCCs arising in these patients progress from endometriotic lesions that may already carry sufficient cancer-associated mutations to be considered neoplasms themselves, albeit with low malignant potential. We speculate that genomically distinct classes of endometriosis exist and that ovarian endometriosis with high mutational burden represents one class at high risk for malignant transformation.
Int Surg. 2015 Feb;100(2):376-80.
Renal endometriosis tends to be misdiagnosed as renal tumor: a rare case report.
Yang J1, Song RJ, Xu C, Zhang SQ, Zhang W.
Renal endometriosis is a rare disease for which the mechanisms of pathogenesis are still unclear. As such, early diagnosis and an appropriate treatment are often delayed because of the tendency to be misdiagnosed as a renal tumor. In October 2013 we performed a radical nephrectomy for a 37-year-old woman with renal endometriosiswho was preoperatively misdiagnosed as having a right renal tumor. Avoiding the misdiagnosis of renal endometriosis requires a detailed case history, especially regarding whether the cyclicity of lumbodorsal pain and hematuria correlates with patients’ menstrual cycles. Imaging examinations are commonly helpful for localization, whereas relieving symptoms with drugs to create a hypoestrogenic state is useful for clinical diagnosis. However, a final diagnosis for renal endometriosis still must depend on histopathologic examination.
J Clin Pharmacol. 2015 Aug;55(8):848-53.
Initiation of GnRH agonist treatment on 3-5 days postoperatively in endometriosis patients: a randomized controlled trial.
Gong L1, Zhang S1, Han Y2, Long Q1, Zou S1, Cao Y1.
Seventy patients with stage III or IV endometriosis were randomly assigned to 2 groups after conservative surgery. Group O (n = 35) received 3 cycles of a 28-day gonadotropin-releasing hormone agonist (GnRH-a) treatment (goserelin, 3.6 mg) starting 3-5 days postoperatively. Group M (n = 35) received the same treatment starting on days 1-5 of menstruation. Groups were further subdivided according to add-back treatment. Pre- and posttreated levels of estradiol (E2 ), follicle stimulating hormone (FSH), and luteinizing hormone (LH) and visual analog scale (VAS), Kupperman menopausal index (KMI), and bone mineral density (BMD) scores were recorded. The incidence of uterine bleeding was assessed. In both groups, serum levels of E2 , FSH, and LH and VAS scores decreased significantly after treatment. Spotting was the most frequent bleeding pattern. During cycle 1, the bleeding time in group M was much longer that than that in group O (P =.001), and the bleeding rate in group M was significantly higher than that in group O (P =.024, RR = 1.185). In patients with stage III or IV endometriosis, the efficacy of GnRH-a initiated 3-5 days postoperatively was equivalent to that of GnRH-a initiated on days 1-5 of menstruation. Female patients who initiated GnRH-a treatment 3-5 days postoperatively experienced less uterine bleeding during the first cycle of treatment.
Int J Gynecol Cancer. 2015 Mar;25(3):440-6.
Clinicopathologic analysis with immunohistochemistry for DNA mismatch repair protein expression in synchronous primary endometrial and ovarian cancers.
Kobayashi Y1, Nakamura K, Nomura H, Banno K, Irie H, Adachi M, Iida M, Umene K, Nogami Y, Masuda K, Kisu I, Ueki A, Yamagami W, Kataoka F, Hirasawa A, Tominaga E, Susumu N, Aoki D.
Synchronous primary endometrial and ovarian cancers have been an important topic in clinical medicine because it is sometimes difficult to distinguish whether there are 2 primary tumors or a single primary tumor and an associated metastasis. In addition, although these tumors are recommended for either immunohistochemistry for DNA mismatch repair (MMR) proteins or a microsatellite instability test in the Bethesda guidelines as Lynch syndrome-associated cancers, few studies have completed these analyses. In this study, we characterized the clinicopathologic features and the expression pattern of MMR proteins in synchronous primary endometrial and ovarian cancers.
Clinicopathologic features and the expression pattern of MMR proteins (MLH1, MSH2, and MSH6) were characterized and analyzed in 32 synchronous primary endometrial and ovarian cancers.
Most synchronous cancers are endometrioid type (endometrioid/endometrioid) (n = 24, 75%), grade 1 (n = 19, 59.4%), and diagnosed as stage I (n = 15, 46.9%) in both endometrium and ovary. It is worth mentioning that 75% of the patients (n = 24) had endometriosis, which was more common (n = 21, 87.5%) in endometrioid/endometrioid cancers, whereas only 3 cases (37.5%) were of different histology (P = 0.018). Loss of expression of at least 1 MMR protein was observed in 17 (53.1%) of the endometrial tumors and in 10 (31.3%) of ovarian tumors. Only 4 cases (12.5%) that had specific MMR protein loss showed the same type of loss for both endometrial and ovarian tumors, in which 3 of the cases were losses in MLH1. One case showed concordant MSH6 protein loss, although the cases did not meet the Amsterdam criteria II.
These results suggest that most synchronous primary endometrial ovarian cancers are not hereditary cancers caused by germ line mutations but rather sporadic cancers.
Int J Gynecol Cancer. 2015 Mar;25(3):447-52.
Increased association between endometriosis and endometrial cancer: a nationwide population-based retrospective cohort study.
Yu HC1, Lin CY, Chang WC, Shen BJ, Chang WP, Chuang CM; Task Force on Carcinogenesis of Endometrial Cancer.
Association between endometriosis and ovarian cancer has been well established. Nonetheless, endometriosis may also be associated with endometrial cancer because of shared etiological mechanisms of both estrogen stimulation and chronic inflammation; however, the association between these 2 disorders has rarely been investigated.
The National Health Insurance Research Databases in Taiwan were retrieved and analyzed. The case cohort consisted of patients with a diagnosis of endometriosis between January 1997 and December 2000 (N = 15,488). For the construction of control cohort, 8 age- and sex-matched control patients for every patient in the case cohort were selected using a random sampling method (n = 123,904). All subjects were tracked for 10 years from the date of entry to identify whether they had developed endometrial cancer. The Cox proportional hazards regression model was used to evaluate 10-year event occurrence of endometrial cancer.
During the 10-year follow-up period, 392 participants developed endometrial cancer, with 104 (0.7%) distributed in the case cohort and 288 (0.2%) in the control cohort. Multivariable Cox regression modeling demonstrates a higher risk for developing endometrial cancer in the case cohort than in the control cohort (adjusted hazard ratio [aHR], 2.83; 95% confidence interval [CI], 1.495.35; P < 0.01). Age at diagnosis of endometriosis shows a moderator effect: when 40 years or younger, the risk for developing endometrial cancer was comparable between the case cohort and the control cohort (aHR, 1.42; 95% CI, 0.55-3.70; P = 0.226), whereas when older than 40 years, the risk for developing endometrial cancer was higher in the former group than in the latter group (aHR, 7.08; 95% CI, 2.33-21.55; P = 0.007).
Patients diagnosed with endometriosis may harbor an increased risk for developing endometrial cancer in their later life. Closer monitoring is advised for this patient population.
Biol Reprod. 2015 Apr;92(4):87.
Identifying the biological basis of GWAS hits for endometriosis.
Fung JN1, Rogers PA2, Montgomery GW3.
Endometriosis is a common estrogen-dependent gynecological disease influenced by multiple genetic and environmental factors. Genome-wide association studies (GWAS) have identified eight genomic regions with strong evidence for association with endometriosis risk and excellent replication in multiple studies. The results represent a significant breakthrough toward understanding endometriosis. However, the significance can be realized only when the associated DNA sequence variation is linked to the altered regulation and/or function of specific genes and pathways modifying endometriosis risk. This review sets out the multiple steps required to interpret the genetic association results, identify the specific genes likely to be responsible for the altered risk within each region, and obtain the necessary genomic evidence connecting the genetic results to the target genes. Strategies include fine mapping, functional annotation, genomics, and target gene identification through gene expression, epigenetics, and cell-based studies to define direct interactions between causal single nucleotide polymorphisms (SNPs) and target genes. To help decode GWAS “hits” affecting endometriosis from multiple regions, there is an urgent need for well-powered genome-wide studies of the regulation of gene expression and epigenetic mechanisms in the endometrium and other reproductive tissues. The system genetics and genomic studies needed to follow-up GWAS signals will also provide insights into gene regulation influencing other reproductive functions. These studies require multidisciplinary research combining genetics, genomics, functional biology, and clinical research to determine the biological pathways responsible and translate the new knowledge into better outcomes for patients.
Eur J Obstet Gynecol Reprod Biol. 2015 Apr;187:6-13
Decreased expression of human heat shock protein 70 in the endometria and pathological lesions of women with adenomyosis and uterine myoma after GnRH agonist therapy.
Khan KN1, Kitajima M2, Hiraki K2, Fujishita A3, Nakashima M4, Masuzaki H2.
A prominent stress reaction in the pelvis of women with endometriosis and the role of human heat shock protein 70 (HSP70) in inflammation and the growth of endometriosis has been recently demonstrated. We report here expression of HSP70 in tissues derived from GnRH agonist (GnRHa)-untreated and -treated women with adenomyosis and uterine myoma.
This is a case-controlled biological study. Biopsy specimens were collected from pathological lesions and eutopic endometria/autologous myometria of 30 women with adenomyosis, 35 women with uterine myoma and 15 control women during laparoscopy, laparotomy and hysteroscopy. Fourteen women with adenomyosis and 20 women with uterine myoma were treated with GnRHa for a variable period of 3-6 months before surgery. The immunoexpressions of HSP70 and CD68-positive Mϕ in endometria, lesions/myometria were examined by immunohistochemistry. The immunoreactivity of HSP70 in tissues was analyzed by quantitative-histogram (Q-H) scores.
Comparing to control women, HSP70 immunoexpression was significantly higher in endometria/myometria and pathological lesions of women with adenomyosis and myoma. A significant positive correlation between Q-H scores of HSP70 and CD68-positive Mϕ numbers was found in the endometria derived from women with adenomyosis (r=0.388). Treatment with GnRHa significantly decreased Q-H scores of HSP70 in pathological lesions and endometria/myometria of women with adenomyosis and uterine myoma comparing to similar tissues derived from GnRHa-untreated women.
A variable amount of tissue stress reaction occurred in endometria and pathological lesions of women adenomyosis and uterine myoma that can be effectively suppressed after GnRHa treatment.
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