Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print] Zearalenone regulates endometrial stromal…
Steroids. 2013 Jun;78(6):555-8. doi: 10.1016/j.steroids.2012.12.002. Epub 2012 Dec 28.
PGRMC2, a yet uncharacterized protein with potential as tumor suppressor, migration inhibitor, and regulator of cytochrome P450 enzyme activity.
PGRMC2 (progesterone receptor membrane component 2) is highly homologous if compared with PGRMC1, a cytochrome-related protein, which is induced in several cancers and linked to cell growth in these cancers. Further it seems to be involved in progesterone signalling and cytochrome P450 binding. For PGRMC2 only sparse information is available. Recent data show that PGRMC1 and 2 share several similar characteristics, but there are also important differences in expression and function of the both proteins. Several findings point to the fact that PGRMC2 might play a role in cancer as well. The protein influences the migration rate of ovarian cancer cells and a loss of PGRMC2 might result in higher metastasis rates. In contrast to PGRMC1 it seems more likely to act as a tumor suppressor than a promoter. Altered PGRMC2 expression was further detected in the context of term and preterm labour, though the implications of this finding are currently unknown and need further examination. PGRMC2 further might play a role in gynaecologic diseases like preterm labour and endometriosis. PGRMC2 shares the cellular localisation and the ability to bind cytochrome enzymes with PGRMC1. Further the protein was shown to influence the activity of CYP3A4. In conclusion, though not much is known about PGRMC2 so far, it deserves further examination as data point to a role of PGRMC2 as tumor suppressor, migration inhibitor and regulator of cytochrome P450 proteins.
Int J Surg Case Rep. 2013;4(2):160-3. doi: 10.1016/j.ijscr.2012.11.007. Epub 2012 Nov 26.
Acute endometrial bowel obstruction-A rare indication for colonic stenting.
Pelvic endometriosis is an extremely rare cause of large bowel obstruction and the management can be challenging. Urgent surgery for acute colonic obstruction is known to carry high morbidity and mortality, and operation may be made more difficult in extensive pelvic endometriosis. Less invasive alternatives in the acute situation may need to be considered.
PRESENTATION OF CASE:
Presented is the case of a 35-year-old lady with obstructive bowel symptoms caused by an endometriotic upper rectal stricture. She was initially treated using radiologically guided stent insertion, as an acute intervention, prior to an elective bowel resection and hysterectomy with bilateral salpingo-oophorectomy.
Colonic stenting is currently widely used in malignant obstruction. The use of self expanding metallic stents (SEMS) to treat benign conditions is controversial, however, due to associated long term complications. This case demonstrates that stenting can provide a bridge to major surgery in the rare event of acute endometriotic colonic obstruction. The initial acute treatment with stenting provides the advantage of time to involve the multi-disciplinary team, to medically optimise the patient and to better plan the definitive surgery.
The use of radiologically guided stents has a place in the treatment of benign recto-sigmoid obstruction due to endometriosis and therefore should be considered as a bridge to further surgical treatment.
Front Biosci (Elite Ed). 2013 Jan 1;5:316-32.
Surgery for deep infiltrating endometriosis: technique and rationale.
The surgical treatment of deep infiltrating endometriosis is challenging and complex. Currently, the gold standard for patient care is the referral to tertiary centers with a multidisciplinary team including gynecologists, colorectal surgeon and urologist with adequate training in advanced laparoscopic surgery. The surgical technique is essential to adequately manage the disease and to minimize the risk of complications; however, the technique is rarely taught and described in details. This paper reviews our current technique and all the tricks to allow the reproduction and even the improvement of this technique by other surgeons.
Front Biosci (Elite Ed). 2013 Jan 1;5:676-83.
Recurrence of endometrioma after laparoscopic excision and its prevention by medical management.
Laparoscopic excision is considered as the ‘gold standard’ treatment of ovarian endometrioma. However, a frustrating aspect is that disease can recur. While laparoscopic excision is known to improve fertility, recurrence can cause significant ovarian damage and adverse affects on fertility. It is therefore crucial to prevent recurrence in order to conserve ‘improved’ fertility. Recurrence rates for endometrioma are reported from 11 to 32% within 1-5 years after excision. The recurrence rate is higher in patients with advanced endometriosis at surgery and in younger patients. Previous medical treatment for endometriosis prior laparoscopy is a risk factor for recurrence. Pregnancy soon after surgery has a protective effect for recurrence. The accumulating evidence suggests that the administration of oral contraceptives (OC), levonorgestrel-releasing intrauterine system (LNG-IUS) and a combination of gonadotropin releasing hormone (GnRH) analogue and OC may also have therapeutic benefits. Collectively, we propose that women should be well informed about the risks of endometrioma recurrence. We recommend that women who wish pregnancy should try conception as soon as possible. Further, we strongly advise hormonal therapy for patients, who do not want to conceive immediately, and until pregnancy is desired.
Front Biosci (Elite Ed). 2013 Jan 1;5:720-4
Effects of early endometriosis on IVF-ET outcomes.
There have been very few reports on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with stage I/II endometriosis. The objective of this study was to investigate IVF-ET outcomes in women with early-stage endometriosis. We enrolled 35 women less than 40 years with unexplained infertility who underwent IVF-ET into the study. We compared 18 women with stage I/II endometriosis according to the revised American Society for Reproductive Medicine classification for endometriosis, who underwent 39 IVF-ET cycles (En (+) group) with 17 women without endometriosis who underwent 41 IVF-ET cycles (En (-) group). Higher requirements of total gonadotropin, a lower percentage of high-quality embryos of all fertilized eggs (9.0% vs. 16.3%), a relatively lower pregnancy rate (33.3% vs. 41.5%), and a lower live birth rate (25.6% vs. 34.1%) were observed in the En (+) group. Although no significant effect on IVF-ET outcome was observed, ovarian response may be decreased in women with stage I/II endometriosis. Considering the decreased number of high-quality embryos in the En (+) group, stage I/II endometriosis may have detrimental effects on embryo quality.
Front Biosci (Elite Ed). 2013 Jan 1;5:748-54.
Association of VEGF +405G>C polymorphism with endometriosis.
The present study was designed to explore the association between the SNP +405G>C of the VEGF gene with the risk of endometriosis, and endometriosis associated with adenomyosis and chocolate cysts. Following extraction of genomic DNA, genotyping of the +405 G>C polymorphisms of the VEGF gene was performed by PCR – RFLP analysis. The genotype (X2 =21.713, 2 df, P = < 0.0001) and allele (X2 =10.697, 1 df, P = 0.0011) frequencies of endometriosis patients were significantly different from those of the control women. The genotype and allele frequencies significantly differed in all the clinical subgroups of endometriosis patients. The significant differences in allele frequencies were the result of an increased proportion of homozygote GG genotype carriers. No significant difference was observed between the clinical subgroups with respect to the genotype and allele frequencies of the VEGF +405G>C polymorphism. These findings suggest that the VEGF +405 G>C polymorphism is associated with the risk of endometriosis, and endometriosis associated with adenomyosis and chocolate cysts.
Mol Cell Endocrinol. 2013 Mar 10;367(1-2):74-84. doi: 10.1016/j.mce.2012.12.019. Epub 2012 Dec 28.
Disturbed balance between phase I and II metabolizing enzymes in ovarian endometriosis: a source of excessive hydroxy-estrogens and ROS?
Oxidative metabolism of estrogens was studied in 31 ovarian endometriosis and 29 normal endometrium samples, by qPCR. Expression was monitored for genes encoding five estrogen hydroxylating, five hydroxy (OH)-estrogen conjugating, and three estrogen quinone detoxifying enzymes. CYP1B1, COMT, NQO1, and GSTP1 protein levels were determined using Western blotting and immunohistochemistry staining. Increased expression of CYP1A1, CYP3A7 and COMT, and higher levels of MB-COMT were seen in endometriosis, as compared to normal endometrium. Expression of CYP1B1, CYP3A5, SULT1A1 and NQO2 was unchanged, with comparable CYP1B1 protein levels. Expression of SULT1E1, SULT2B1, UGT2B7, NQO1, and GSTP1 was decreased. Three NQO1 isoforms were detected; NQO1c appears to be endometriosis-specific. Our data indicate a disturbed balance between phase I and II metabolizing enzymes in endometriosis, potentially leading to excessive OH-estrogen and altered ROS formation, and stimulation of proliferation of ectopic endometrium. This is the first report on disturbed expression of estrogen oxidative metabolism genes in ovarian endometriosis.
Syst Biol Reprod Med. 2013 Apr;59(2):91-8. doi: 10.3109/19396368.2012.743197. Epub 2013 Jan 2.
Oxidative status in granulosa cells of infertile women undergoing IVF.
Studies on elevated reactive oxygen species (ROS) levels in granulosa cells (GC) and its subsequent effect on fertilization are limited. Oxidative stress (OS) mediated alterations in GC of infertile women undergoing in vitro fertilization (IVF) and embryo transfer (ET) was investigated. GC were obtained from 28 women with endometriosis (Group A), 26 women with polycystic ovary syndrome (PCOS) (Group B), and 32 women with tubal factor infertility (Group C). GC characteristics including cell count, viability, morphology and number of oocytes retrieved, and oocyte quality were assessed. OS parameters such as ROS, mitochondrial membrane potential (MMP), and DNA fragmentation were also studied and IVF outcome parameters assessed. An ∼20 fold increase in GC ROS generation was observed in Group B as compared to Group C. Though not as high as Group B, Group A also showed significantly high ROS levels compared with Group C. More than 100-fold decrease in MMP in Group B compared with Group C was observed. A similar trend was observed in Group A, where MMP decreased 7 fold. Significant apoptosis was evident in Groups A and B supported by depolarization of MMP and significant increase in DNA damage. IVF outcome parameters including fertilization rate, good quality embryo formation rate, and pregnancy outcome were adversely affected in Group B. It is hypothesized that ∼20 fold increase in ROS generation in GC of PCOS women plays an adverse role in affecting the IVF success rate. It was of note that the IVF outcome parameters of women with endometriosis were not affected.
Am J Surg Pathol. 2013 Mar;37(3):356-67. doi: 10.1097/PAS.0b013e318272ff19.
Clinicopathologic analysis of low-stage sporadic ovarian carcinomas: a reappraisal.
Current histologic criteria endorsed by World Health Organization for surface epithelial ovarian tumors suffer from less than optimal reproducibility and correlation with clinical outcomes. A modified approach for histologic subclassification of ovarian carcinomas (OCs), proposed by the group of Gilks and colleagues, has been shown to be reproducible and clinically meaningful. We hypothesized that this approach could be validated using a well-annotated, external cohort of OCs with detailed immunophenotypic, genotypic, and clinical data. The cohort comprised 91 patients with low-stage (FIGO stage I/II) OC who underwent primary surgical management at our institution from 1980 to 2000. The clinical and histologic features of this cohort were reported in 2004. In this study we rereviewed the hematoxylin and eosin slides and reassigned histologic type using the criteria proposed by Gilks and colleagues. p53 and Wilms tumor 1 (WT1) expressions were evaluated using standard immunohistochemical techniques on a tissue microarray. Absence of (null) or strong and diffuse p53 staining in >75% of tumor cells (overexpression) was interpreted as aberrant p53 expression, in contrast to the 2004 study in which the “null” result had been interpreted as negative. Direct TP53 gene sequencing of the entire coding region had been performed on all cases with available tissue. Relationships between survival and the following parameters were studied: tumor cell type, histologic grade, stage, p53 and WT1 expression, TP53 mutation, and presence of associated endometriosis. Results were compared with those of the 2004 study, at which time only TP53 mutation was shown to correlate with adverse survival; notably, TP53 mutation did not correlate with p53 expression by immunohistochemical analysis. After review, presence of TP53 mutations, WT1 positivity, and aberrant p53 expression were strongly associated with high-grade serous histology (P=0.0001). Modification of p53 staining assessment revealed strong correlations with TP53 mutation status, which was superior to the positive versus negative approach used previously (P=0.0005). Redefined histologic criteria revealed a stronger association between the high-grade serous type and WT1 positivity (P=0.02). Prolonged 10-year disease-specific and progression-free survival were associated with endometrioid histology (P<0.02; 94%±4% vs. 53%±7% and 96%±4% vs. 50%±7%, respectively). Inferior 10-year disease-specific survival and progression-free survival were associated with high histologic grade (vs. low and intermediate; P<0.01; 54%±7% vs. 89%±6% and 56%±7% vs. 89%±6%, respectively), presence of TP53 mutation (P<0.04; 54%±12% vs. 64%±10% and 34%±12% vs. 70%±6%, respectively), aberrant p53 expression (P<0.02; 35%±12% vs. 75%±7% and 36%±12% vs. 73%±7%, respectively), and absence of associated endometriosis (P=0.01; 48%±9% vs. 80%±6% and 51%±9% vs. 80%±6%, respectively). In addition, inferior 10-year PFS was associated with WT1 positivity (P=0.01; 42%±7% vs. 72%±7%) and high substage (IA-IB vs. IC-IIC; P=0.04; 53%±7% vs. 81%±8%). These results validate updated approaches to scoring p53 expression as well as the revised criteria proposed by the group of Gilks and colleagues.
Biol Reprod. 2013 Feb 21;88(2):44. doi: 10.1095/biolreprod.112.104497. Print 2013 Feb.
Changes in eutopic endometrial gene expression during the progression of experimental endometriosis in the baboon, Papio anubis.
Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons (n = 4) by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected during the midsecretory phase (Days 9-11 postovulation) at 1, 3, 6-7, 10-12, and 15-16 mo after disease induction and compared with tissue from disease-free baboons. RNA was hybridized to Human Genome U133 Plus 2.0 Arrays, and data were extracted using Gene-Chip Operating Software. Subsequently, both Gene Set Enrichment Analysis and Ingenuity Pathways Analysis were used to find biological states that have a statistically significant enrichment concomitant with pairwise comparison of human endometriosis arrays. Within 1 mo of induction of the disease, 4331 genes were differentially expressed (P < 0.05). Hierarchical clustering revealed self-segregation into two groups-a) 1, 3, and 10-12 mo and b) 6-7 and 15-16 mo-together with controls. Clustering analysis at each stage of disease validated dysregulation of several signaling pathways, including Nodal-like receptor, EGF, ERK/MAPK, and PI3/AKT. Sequential analysis of the same animals during disease progression demonstrated an early disease insult and a transitory dominance of an estrogenic phenotype; however, as the disease progressed, a progesterone-resistant phenotype became evident. Furthermore, we demonstrate a 38.6% differential gene expression overlap with endometrial samples in the midsecretory phase from women with endometriosis, concomitant with similar dysregulation in human disease candidate genes Fos, Nodal, Suclg2, and Kras, among others. Molecular changes in the eutopic endometrium, associated with endometriosis, are directly impacted by endometriotic lesions, providing strong evidence that it is the disease rather than inherent defective endometrium that results in aberrant gene expression in the eutopic endometrium. Furthermore, this baboon model provides a powerful means whereby the early events associated with the pathology of disease and the resulting infertility may be elucidated.
Reprod Sci. 2013 Jun;20(6):688-98. doi: 10.1177/1933719112466301. Epub 2013 Jan 3.
Oxidative cell injury as a predictor of endometriosis progression.
There is increasing evidence that oxidative stress is one of the key factors for progression of endometriosis. In this prospective controlled trial, we measured 6 different biomarkers of oxidative stress targeting protein, lipid, and DNA to quantify the severity and progression of endometriosis and establish a diagnostic marker for the disease.
A total of 62 consecutive patients were identified and enrolled in this study. After exclusion criteria, 44 patients were allocated to 3 groups: stage I/II (n = 14), stage III/IV (n = 16), and a control group (n = 14). The levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), 8-oxoguanine DNA glycosylase (OGG1), protein carbonyl (PC), lipid peroxidation (LPO), reactive oxygen species (ROS), and total antioxidant capacity (TAC) were accessed in peritoneal fluid and tissue.
Significantly higher levels of 8-OHdG and PC were seen in patients with endometriosis, in addition OGG1 expression was found to be significantly lower in patients with endometriosis (P < .001, P = .001, P = .033, respectively); ROS, TAC, and LPO were similar in stages I/II, stages III/IV, and control group. A predictive model was built using multivariable analyses and receiver-operating characteristics curves. The ability to predict and distinguish between patients without endometriosis, stage I/II endometriosis, and stage III/IV was very high. This model was highly discriminatory and had a concordance index of 0.87.
In this cohort, higher DNA damage and lower DNA repair activity was related to endometriosisprogression. Our results indicate that oxidative stress as a biomarker of cell injury can be used as a reliable quantitative test of endometriosis severity.
J Bras Pneumol. 2012 Nov-Dec;38(6):797-802. English, Portuguese.
Pleural endometriosis: findings on magnetic resonance imaging.
Endometriosis is a benign gynecological disorder associated with pelvic pain and infertility, primarily affecting women of reproductive age. Thoracic endometriosis affects the pulmonary parenchyma or pleura. We report the cases of two patients with pleural endometriosis who presented with recurrent pneumothorax. In both cases, magnetic resonance imaging (MRI) of the chest showed right hydropneumothorax and well-defined, rounded nodules on the pleural surface in the right hemithorax. We conclude that MRI is a good option for the characterization of pleural endometriotic nodules and hemorrhagic pleural effusion.
J Vis Exp. 2012 Dec 21;(70). pii: 4313. doi: 10.3791/4313.
Intraoperative detection of subtle endometriosis: a novel paradigm for detection and treatment of pelvic pain associated with the loss of peritoneal integrity.
Endometriosis is a common disease affecting 40 to 70% of reproductive-aged women with chronic pelvic pain (CPP) and/or infertility. The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surfaces during laparoscopy (L/S) to detect the loss of peritoneal integrity in patients with pelvic pain and suspected endometriosis. Forty women with CPP and 5 women without pain were evaluated in this pilot study. During L/S, concentrated dye was sprayed onto peritoneal surfaces, then aspirated and rinsed with Lactated Ringers solution. Areas of localized dye uptake were evaluated for the presence of visible endometriotic lesions. Areas of intense peritoneal staining were resected and some fixed in 2.5% buffered gluteraldehyde and examined by scanning (SEM) electron microscopy. Blue dye uptake was more common in women with endometriosis and chronic pelvic pain than controls (85% vs. 40%). Resection of the blue stained areas revealed endometriosis by SEM and loss of peritoneal cell-cell contact compared to normal, non-staining peritoneum. Affected peritoneum was associated with visible endometriotic implants in most but not all patients. Subjective pain relief was reported in 80% of subjects. Based on scanning electron microscopy, we conclude that endometrial cells extend well beyond visible implants of endometriosis and appear to disrupt the underlying mesothelium. Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity, allowing menstrual or ovulatory blood and associated pain factors access to underlying sensory nerves. Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP. This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at L/S and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy.
Fertil Steril. 2013 Apr;99(5):1332-1339.e5. doi: 10.1016/j.fertnstert.2012.11.033. Epub 2013 Jan 3.
Expression of the pluripotent transcription factor OCT4 promotes cell migration in endometriosis.
To identify the impact of the pluripotent transcription factor OCT4 in endometrial cell migration and endometriosis.
The OCT4 expression and cell migration study.
Research institution and reproductive medical clinic.
Nine subjects with normal endometrium, 3 subjects with normal myometrium, 36 patients with hyperplastic endometrium, and 58 patients with endometriosis.
The expression of OCT4 messenger RNA in normal endometrium, normal myometrium, hyperplastic endometrium, and ectopic endometriotic tissues was analyzed using reverse transcription and quantitative real-time polymerase chain reaction (PCR). The effect of OCT4 expression on the migration activity of the endometrial cells was examined.
MAIN OUTCOME MEASURE(S):
Reverse transcription and quantitative real-time PCR, Western blotting, and wound closure and transwell assays.
The expression of OCT4 and NANOG messenger RNA was significantly higher in ectopic endometriotic tissues, compared with that of the normal endometrium, the normal myometrium, and the hyperplastic endometrium. The level of OCT4 messenger RNA in endometriotic tissues was positively correlated with the expression of genes associated with cell migration. Overexpression of the OCT4 protein in primary human endometriotic stromal cells and human RL95-2 and HEC1A endometrial carcinoma cell lines resulted in decreased levels of E-CADHERIN, the increased expression of the VIMENTIN, TWIST, and SLUG proteins, and an increase in the migration activity of endometrial cells in transwell and wound closure assays.
The transcription of the OCT4 gene is significantly up-regulated in human ectopic endometriotic tissues. The expression of OCT4 may contribute to the pathology of ectopic endometrial growth by stimulating the migration activity of endometrial cells.
Gynecol Obstet Fertil. 2013 Jan;41(1):58-64. doi: 10.1016/j.gyobfe.2012.12.002. Epub 2013 Jan 3. French.
Multidisciplinary approach for deep endometriosis: interests and organization.
Deep endometriosis is a frequent disease that affects reproductive age women. This disease is characterized by the presence of functional endometrium-like tissue outside the uterus. The common sites of extragenital endometriosis are the bowel and the urinary tract. This disease is also associated with infertility. Furthermore, this disease can cause physical and psychological damage. Therefore, it is really important to develop a multidisciplinary approach in the aim to offer the appropriate treatment. The multidisciplinary team approach for endometriosis is developing to improve the understanding of endometriosis and a multidisciplinary committee for endometriosis was developed in our center. During this meeting, gynecologic, digestive surgeons, urologist, radiologist, procreative medical assistance physicians analyse the case. The role of surgery, before, after or as an alternative to in vitro fertilization (IVF) must be defined. The role of the medical treatment before or after the surgery, before the IVF shall be discussed in order to propose the optimal treatment. In fact, radical surgery is no more recommended and minimally invasive conservative surgery is encouraged in order to preserve the fertility. The multidisciplinary approach permits an appropriate optimal and personalised management of this multifocal disease. The multidisciplinary team approach helps in the development of evidence-based guidelines for the diagnosis and management of endometriosis.
Gynecol Obstet Fertil. 2013 Jan;41(1):38-44. doi: 10.1016/j.gyobfe.2012.11.010. Epub 2013 Jan 3. French.
Female sexuality after surgical treatment of symptomatic deep pelvic endometriosis.
The aim of this study is to assess the impact on sexuality of the surgical treatment in patients with symptomatic deep pelvic endometriosis.
PATIENTS AND METHODS:
The design is a single-center cohort prospective study including all patients with symptomatic pelvic endometriosis and regular sexual activity who underwent surgery between October 2009 and September 2010. Sexual function was evaluated by the “Brief Index of Sexual Functioning for Women” (BISF-W) questionnaire translated and validated in French, including a global evaluation by the Composite Score (CS). Pain symptoms related to endometriosis were evaluated by the Visual Analog Scale (VAS) and the simple Verbal Rating Scale (VRS). Questionnaires were answered before surgery. A standardized mid and long-term postoperative follow-up was performed to compare sexuality and pain symptoms.
Twenty women were included in the study. Mean follow-up was 23.3 months. When compared to a French reference population, global preoperative sexual function was significatively deteriorated (CS=14.3±10.8 vs 32.2±12.6; P<0.001), especially for arousal, frequency of sexual activity, pleasure and orgasm. Significant improvements in sex life were observed after surgery at the long-term follow-up (CS=33.0±11.7 vs 14.3±10.8; P=0.02). and sexual function was similar to the reference population (CS=33.0±11.7 vs 32.2±12.6; P=0.806). At the mid-follow-up, a significant improvement in the intensity of dysmenorrhoea, non-cyclic pelvic pain, dyspareunia and bowel symptoms were observed on the VAS. At the long-term follow-up, dysmenorrhoea and dyspareunia were significatively ameliorated. Pelvic pain recurrence related to endometriosis was 13.3%.
DISCUSSION AND CONCLUSION:
Surgical management of deep pelvic endometriosis in symptomatic patients improves sexual life at the long term follow-up. Deep dyspareunia pain decreases significantly, although other conditions are involved in the improvement of sexual function.
Best Pract Res Clin Obstet Gynaecol. 2013 Jun;27(3):431-40. doi: 10.1016/j.bpobgyn.2012.11.004. Epub 2013 Jan 3.
New developments in reproductive surgery.
The introduction of in-vitro fertilisation within reproductive medicine has prompted questions to be asked about the relevance of reproductive surgery. Reproductive surgery is more than a competing discipline; it is complementary to the techniques of in-vitro fertilisation. As a complementary discipline, reproductive surgery covers the field of tubal and ovarian pathology and correction of uterine alterations. In recent decades, more attention has been paid to the importance of the uterus in the process of conception and implantation. The place of reproductive surgery and the existing controversies in the treatment of uterine congenital and acquired pathology, tubal, and ovarian surgery are discussed. Continuous training and accreditation programmes for reproductive technologies and surgery are more important than ever.
Arch Gynecol Obstet. 2013 Jun;287(6):1251-7. doi: 10.1007/s00404-012-2704-9. Epub 2013 Jan 6.
Can ovarian damage be reduced using hemostatic matrix during laparoscopic endometrioma surgery? A prospective, randomized study.
To compare the effect of hemostatic matrix (HM) and electrosurgical bipolar coagulation (EBC) on ovarian reserve in patients undergoing endometrioma surgery.
Thirty patients with single ovarian endometrioma ≥4 cm were randomized to two groups. Ovarian reserve after laparoscopic excision of endometrioma was assessed by serum anti-Müllerian hormone (AMH); preoperatively and in postoperative months 1 and 3.
The preoperative AMH levels were similar between the groups. Intra-group comparisons: the AMH levels were significantly lower in the first and third postoperative months as compared to basal levels in both groups. In each group, AMH levels were significantly higher in the third postoperative month as compared to first postoperative month. Inter-group comparisons: AMH levels were significantly lower in the EBC as compared to the HM at 1st postoperative month (1.64 ± 0.93 vs. 2.72 ± 1.49 ng/mL). However, the AMH levels were increased and became similar at 3rd postoperative month.
Although acute ovarian damage was more in EBC group, ovarian reserve was compensated at 3rd month. Further studies with long-term follow-up will clarify the importance of these findings.
Chin J Integr Med. 2013 Nov;19(11):820-5. doi: 10.1007/s11655-012-1247-z. Epub 2012 Dec 22.
Controlling the recurrence of pelvic endometriosis after a conservative operation: comparison between Chinese herbal medicine and western medicine.
To compare the clinical effect of Chinese medicine (CM) and Western medicine (WM) for controlling the recurrence of pelvic endometriosis after a conservative operation.
The study was a multi-center, randomized, parallel controlled and prospective clinical trial. Patients were randomly divided into two groups: CM group (106 cases) and WM group (102 cases). Drugs were given to patients during 1-5 days of the first menstruation after a conservative operation in both groups. Patients with stages I and II (revised American Fertility Society) were treated for 3 months, while the patients with stages III and IV were treated for 6 months. The patients in the CM group were treated using three types of Chinese herbal medicine based on syndrome differentiation. Patients in the WM group were treated using gonadotropin releasing hormone agonist (GnRH-a) or gestrinone. Patients treated with GnRH-a received add-back therapy of Tibolone Tablets once a day after 4 months of treatment. Any cases of dysmenorrheal chronic pelvic pain, menstruation and any adverse reactions of patients were recorded once a month during the preoperative and postoperative periods and once every 3 months during the follow-up period. During the preoperative, postoperative and the follow-up periods, patients underwent type B ultrasonography of the pelvis and measurements of serum CA125 levels, gynecologic examination, routine evaluations of blood, urine, hepatic function (glutamate pyruvate transaminase), renal function (blood urea nitrogen) and electrocardiograms. During the follow-up period they underwent type B pelvic ultrasonography, measurement of serum CA125 levels and further gynecologic examinations. The two treatments were compared for clinical recurrence rates, pregnancy rates and the incidence of adverse reactions.
The incidence and timing of recurrence of endometriosis were not significantly different between the two groups. The first pregnancy achieved by the patient in the CM group was significantly earlier than that in the WM group (P <0.05). Moreover, the incidence of adverse reactions in the WM group was significantly higher than in the CM group (P <0.01).
Treatment with Chinese herbal medicines prevented the recurrence of endometriosis after a conservative operation, improved the conception rate and showed fewer and lighter adverse reactions than did treatment with WM therapy. Treatment with Chinese herbal medicine meets the need of patients wishing to have a child following endometriosis and is an appropriate form of clinical treatment.
Hum Reprod. 2013 Mar;28(3):750-61. doi: 10.1093/humrep/des446. Epub 2013 Jan 4.
miR-196b targets c-myc and Bcl-2 expression, inhibits proliferation and induces apoptosis in endometriotic stromal cells.
What is the global expression pattern of microRNAs (miRNAs) in endometriotic stromal cells and is miR-196b involved in the pathogenesis of endometriosis?
Several miRNAs are aberrantly expressed in endometriotic cyst stromal cells (ECSCs), including miR-196b whose expression is repressed in endometriotic stromal cells.
WHAT IS KNOWN ALREADY:
Although, histologically, endometriotic tissues and normal proliferative endometrium are similar, a number of distinct molecular differences have been reported to date. The anti-apoptotic and excessive proliferative properties of endometriotic cells are considered to be involved in the development and progression of endometriosis.
STUDY DESIGN AND SIZE DURATION:
ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues and eutopic endometrial tissues, respectively and compared.
PARTICIPANTS/MATERIALS, SETTING AND METHODS:
Aberrantly expressed miRNAs in ECSCs were identified by a global miRNA microarray technique. The roles of miR-196b in ECSC proliferation, apoptosis, and c-myc and B-cell lymphoma/leukemia (Bcl)-2 mRNA expression were investigated with precursor hsa-miR-196b transfection. The methylation status of the miR-196b gene in ECSCs and the effect of a DNA demethylating agent on miR-196b expression were also examined.
MAIN RESULTS AND THE ROLE OF CHANCE:
miRNA microarray analysis identified eight down-regulated miRNAs (including miR-196b) and four up-regulated miRNAs in ECSCs. Compulsory expression of miR-196b directed the inhibition of proliferation and the induction of apoptosis in ECSCs. miR-196b was found to suppress c-myc and Bcl-2 mRNA expression in ECSCs, and there was a significant correlation between miR-196b and HOXA10 expression in ECSCs and NESCs. The miR-196b gene was hypermethylated in ECSCs when compared with NESCs, and the treatment with a DNA demethylating agent restored the expression of miR-196b in ECSCs.
LIMITATIONS AND REASONS FOR CAUTION:
miRNA expression profiles were investigated only in the stromal component of ectopic and eutopic endometrium samples. In addition to miR-196b, the roles of other miRNAs aberrantly expressed in ECSCs should be examined.
WIDER IMPLICATIONS OF THE FINDINGS:
The present findings suggest that aberrant miRNA expression plays an important role in the pathogenesis of endometriosis as a part of epigenetic mechanisms, that expression of miR-196b in ECSCs is repressed by DNA hypermethylation of the miR-196b gene and this repression may be involved in the development of proliferative and anti-apoptotic characteristics of endometriosis.
This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 20591920 to K.N. and no. 23592407 to H.N.) and The Uehara Memorial Foundation (to K.N.).
J Clin Endocrinol Metab. 2013 Feb;98(2):E238-48. doi: 10.1210/jc.2012-2969. Epub 2013 Jan 4.
Regulation of P21-activated kinase-4 by progesterone and tumor necrosis factor-α in human endometrium and its increased expression in advanced-stage endometriosis.
Endometriosis is a common gynecological condition characterized by enhanced proliferation, adhesiveness, invasiveness, and survival of endometrial cells after retrograde menstruation. Originally identified as a cytoskeletal regulatory kinase, p21-activated kinase 4 (Pak4) regulates diverse cellular activities that might be altered in the establishment and progression of endometriosis.
The aim was to evaluate the effects of sex steroids and proinflammatory cytokines on the Pak4 expression in endometrial cells along with the functional change caused by inhibition of Pak4 expression as well as to see whether the Pak4 expression is altered in endometriosis.
Pak4 expression was analyzed using immunohistochemistry and Western blot analysis. Viability and invasiveness were assayed after transfection of endometrial cells with Pak4 small interfering RNA.
The Pak4 expression was significantly decreased in the stromal cells during the secretory phase as well as by in vitro treatment with progesterone. The immunoreactivity of Pak4 was significantly increased in the eutopic endometrium as well as in the ovarian endometriotic cyst of women with endometriosis compared with the control subjects. TNF-α induced a significant increase in the Pak4 expression in endometrial cells in vitro, whereas IL-1β had no effects. Transfection of endometrial cells with Pak4 small interfering RNA led to a significant decrease in viability and invasiveness in endometrial cells.
These findings suggest that Pak4 is regulated by progesterone and TNF-α in endometrial cells and that the increased expression of Pak4 might lead to the establishment and progression of endometriosis by enhanced cellular viability and invasiveness in endometrial cells.
Int J Clin Pract. 2013 Mar;67(3):225-35. doi: 10.1111/ijcp.12031. Epub 2013 Jan 7.
Vitamin D in human reproduction: a narrative review.
Special attention has been given to the effect of vitamin D supplementation on fertility outcomes in both sexes.
The purpose of this narrative review was to elucidate the role of vitamin D in male and female reproduction, providing current evidence from both animal and human studies.
MATERIALS AND METHODS:
Using PubMed and Medline, we searched for publications during the last 30 years regarding the role of vitamin D in human reproduction.
Accumulating evidence from animal and human studies suggests that vitamin D is involved in many functions of the reproductive system in both genders. In women, vitamin D status has been associated with in vitro fertilization (IVF) outcome, features of polycystic ovarian syndrome (PCOS) and endometriosis. Although several data converge towards a beneficial effect of vitamin D supplementation in metabolic disturbances in women with PCOS, a significant knowledge gap precludes the establishment of a clear cause-effect relationship. In men, vitamin D status has been associated with semen quality and sperm count, motility and morphology. There is evidence for a favourable effect of vitamin D supplementation on semen quality, testosterone concentrations and fertility outcomes.
Studies with superior methodological characteristics are needed in order to establish a role for vitamin D on the treatment of female and male infertility.
Recent data on vitamin D provide new insights in the complex pathogenesis and treatment of infertility.
Niger J Med. 2012 Jan-Mar;21(1):108-10.
Asymptomatic incisional endometrioma presenting as abdominal wall mass: a case report.
Asymptomatic incisional endometrioma of the anterior abdominal wall is rare. Clinical diagnosis may be difficult. We present a 26-year-old woman with incisional abdominal wall endometrioma discovered 5 years after caeserian section. It was painless and there was no change in size with menstruation. The patient’s body size was average with a palpable lump at the edge of the caeserian section scar. Clinically desmoid tumour was suspected. The patient underwent surgical excision. Histopathology confirmed endometrioma. There was no recurrence on three months follow-up.
Zhonghua Fu Chan Ke Za Zhi. 2012 Nov;47(11):823-8. Chinese.
Related factors associated with pelvic adhesion and its influence on fallopian tube recanalization in infertile patients.
To investigate factors with pelvic adhesions and the effect of different degrees pelvic adhesions on fallopian tube recanalization in infertile patients.
Total of 527 infertile patients undergoing hysteroscopy and laparoscopic surgery in Affiliated Hospital of Chinese People’s Armed Police Forces Logistics College were studied retrospectively. According to the extent of pelvic adhesions, tubal umbrella adhesions and atresia, 377 cases were classified into adhesion groups, including 73 cases in grade I, 221 cases in grade II, 75 cases in grade III and 8 cases in grade IV based on adhesion score. The 150 cases with no obvious pelvic adhesion were matched as control group. Among 8 cases with grade IV ahesion were exluded from ahesion group the relationship between pelvic adhesions and related history, abdominal lesions, tubal patency and the prognosis were studied.
(1) Related factors: the frequency of pelvic adhesion and more than 7 years of infertility of 23.9% (88/369) in adhesion group were significantly higher than 12.0% (18/150) in control groups. (2) HISTORY: compared with the control group (12.7%, 19/150; 28.7%, 43/150; 11.3%, 17/150; 12.0%, 18/150; 17.3%, 26/150), patients with pelvic adhesions present more incidence abortion (23.6%, 87/369), uterine cavity operation (38.2%, 141/369), ectopic pregnancy (20.9%, 77/369), pelvic inflammatory disease (25.5%, 94/369) and abdominopelvic surgery (31.4%, 116/369). (3) Endoscopy exploration: the incidence of hydrosalpinx (24.7%, 91/369), tube distorted (15.7%, 58/369) and salpingostomy (72.9%, 269/369) in adhesion group were higher than those in control group (2.0%, 3/150; 4.0%, 6/150; 12.0%, 18/150), but relatively lower incidence of pelvic endometriosislesions (5.7%, 21/369) and mesosalpinx cysts (16.3%, 60/369) than those in control group (16.0%, 24/150; 30.0%, 45/150). The rate of proximal tubal recanalization (59.5%, 91/153) in adhesion group was lower than 75.4% (52/69) in control group. However, the rate of distant tubal recanalization of 84.4%, (281/333) in adhesion group and; 13/15 in control group didn’t show statistical difference. (4) PROGNOSIS: the rate of ectopic pregnancy of 9.7% (29/299) in adhesion group was significantly higher than 3.1% (4/128) in control group. Among cases with grade III adhesion exhibited the highest rate of ectopic pregnancy (13.0%, 7/54; OR = 4.62, 95%CI: 1.29 – 16.50). (5) Multivariate analysis: it was found that more than two drug abortions (OR = 3.29, 95%CI: 1.34 – 8.07), pelvic and(or) abdominal surgery history (OR = 2.20, 95%CI: 1.35 – 3.57) and pelvic inflammatory disease history (OR = 1.54, 95%CI: 1.21 – 1.97) were risk factors with pelvic adhesions.
More than or equal to two drug abortion history, pelvic inflammatory disease and pelvic and abdominal surgery damage were important factors for pelvic adhesions of infertility patients, which may decrease the possibility of proximal tubal recanalization and increase ectopic pregnancy risk.
Zhonghua Fu Chan Ke Za Zhi. 2012 Nov;47(11):829-32.
Study on pathological characteristics of eutopic endometrium in endometriosis.
To study the pathologic characteristics of eutopic endometrium in patients with endometriosis.
Pathologic characteristics of eutopic endometrium were studied in 176 patients with endometriosis in Peking Union Medical College Hospital from January 2007 to December 2008 retrospectively.
About 72.2% (127/176) of eutopic endometrium were in proliferative phase, 19.9% (35/176) of were observed as endometrial polyp, including 32 cases with simple endometrial polyp and 3 cases with abnormal hyperplasia combined with endometrial polyp. And 4.0% (7/176) showed abnormal hyperplasia. The incidence of pathologic changes in eutopic endometrium was 22.2% (39/176). Among 53 endometriosis patients combined with infertility, the incidence of pathologic changes of eutopic endometrium was 35.9% (19/53), which was significantly higher than 16.3% in non-infertile patients (χ(2) = 8.24, P = 0.004). Among 65 cases with irregular menstruation, the incidence of endometrial polypus and endometrial hyperplasia were 20.0% (13/65) and 10.8% (7/65), which were significantly higher than 17.1% (19/111) and 0 in normal menstruation patients (χ(2) = 13.839, P = 0.003).
The eutopic endometrium of endometriosis were in proliferative phase state. The pathologic changes of eutopic endometrium were more in patients combined with infertility and irregular menstruation.
Reprod Sci. 2013 Aug;20(8):998-1002. doi: 10.1177/1933719112472743. Epub 2013 Jan 9.
RHOC: a key gene for endometriosis.
Considerable efforts have been invested in elucidating the potential mechanisms involved in the physiopathology of endometriosis. The aims of our study were to investigate whether RHOC expression is differentially altered in the endometrium and in endometriotic lesions. A total of 40 patients diagnosed with endometriosis and 15 healthy fertile women were selected for the study. Paired biopsies of endometrial tissue (eutopic endometrium) and endometriotic lesions (ectopic endometrium) were obtained from the patients with endometriosis. Endometrium from women without endometriosis was used as a control. Expression of the RHOC gene was analyzed by real-time polymerase chain reaction in autologous endometrial tissues of women with endometriosis and in the endometrium of control women. Increased RHOC expression was detected in endometriotic lesions compared to the eutopic endometrium of women with endometriosis and control women. RHOC changes may be among the key elements involved in the origin and the maintenance of endometriosis.
Endocr Rev. 2013 Feb;34(1):130-62. doi: 10.1210/er.2012-1043. Epub 2013 Jan 9.
Progesterone action in endometrial cancer, endometriosis, uterine fibroids, and breast cancer.
Progesterone receptor (PR) mediates the actions of the ovarian steroid progesterone, which together with estradiol regulates gonadotropin secretion, prepares the endometrium for implantation, maintains pregnancy, and differentiates breast tissue. Separation of estrogen and progesterone actions in hormone-responsive tissues remains a challenge. Pathologies of the uterus and breast, including endometrial cancer, endometriosis, uterine fibroids, and breast cancer, are highly associated with estrogen, considered to be the mitogenic factor. Emerging evidence supports distinct roles of progesterone and its influence on the pathogenesis of these diseases. Progesterone antagonizes estrogen-driven growth in the endometrium, and insufficient progesterone action strikingly increases the risk of endometrial cancer. In endometriosis, eutopic and ectopic tissues do not respond sufficiently to progesterone and are considered to be progesterone-resistant, which contributes to proliferation and survival. In uterine fibroids, progesterone promotes growth by increasing proliferation, cellular hypertrophy, and deposition of extracellular matrix. In normal mammary tissue and breast cancer, progesterone is pro-proliferative and carcinogenic. A key difference between these tissues that could explain the diverse effects of progesterone is the paracrine interactions of PR-expressing stroma and epithelium. Normal endometrium is a mucosa containing large quantities of distinct stromal cells with abundant PR, which influences epithelial cell proliferation and differentiation and protects against carcinogenic transformation. In contrast, the primary target cells of progesterone in the breast and fibroids are the mammary epithelial cells and the leiomyoma cells, which lack specifically organized stromal components with significant PR expression. This review provides a unifying perspective for the diverse effects of progesterone across human tissues and diseases.
Case Rep Med. 2012;2012:497362. doi: 10.1155/2012/497362. Epub 2012 Dec 4.
Malignant transformation of endometrioma in a woman with a history of ovulation induction and in vitro fertilization.
Our aim is to document a case of endometrioid adenocarcinoma of the ovary found in an endometriotic cyst that was suspected on pelvic ultrasound in a patient with polycystic ovary syndrome, normal Ca125, and a recent history of ovulation induction for IVF. She underwent an exploratory laparotomy with left salpingo-oophorectomy and omental biopsies followed by reexploration, complete staging, and modified radical abdominal hysterectomy and right salpingo-oophorectomy. An endometrioma described as suspicious for malignancy by an experienced ultrasound examiner should prompt immediate referral to a gynecological oncologist irrespective of Ca125 levels especially in women with a history of ovulation induction and endometriosis.
J Thorac Dis. 2012 Nov;4 Suppl 1:17-31. doi: 10.3978/j.issn.2072-1439.2012.s006.
Catamenial pneumothorax: a rare entity? Report of 5 cases and review of the literature.
Spontaneous recurrent pneumothorax during menstruation is reported as catamenial pneumothorax. It is encountered in 3-6% of spontaneous pneumothorax cases among menstruating women. The percentage among women referred for surgery is significantly higher (25-30%). Although it usually involves the right-side (85-95%) it can be left-sided or bilateral. It is associated with diaphragmatic perforations and/or thoracic endometriosis. There is pelvic endometriosis in up to 30-51% of cases. The lesions that are not always found may present as small or larger holes at the central tendon of the diaphragm, as red, blueberry, brown spots or larger nodules at the diaphragm, the visceral or parietal pleura. Lesion histology may reveal endometriosis. We present 5 cases of catamenial pneumothorax treated surgically during the last 6 years.
PATIENTS AND METHODS:
Five women, with a mean age of 34+/-9.9 years (median 38, range, 19-45 years) presented with right-sided recurrent catamenial pneumothorax. In 3 patients diaphragmatic perforation(s) were found; perforation suturing (n=1), and diaphragmatic plication reinforced with bovine pericardial patch (n=1) were performed. All patients underwent atypical resection of upper and/or middle lobe segments of lung parenchyma that appeared abnormal (haemorrhagic/emphysematous or blebs). Four patients underwent pleurodesis and 1 patient underwent pleurectomy. Four interventions were performed through video assisted thoracoscopic surgery, while diaphragmatic plication was performed through a video assisted mini-thoracotomy. Histology did not reveal endometriosis tissue.
The postoperative course was uneventful. The patients were extubated in theatre and were discharged home at a mean of 7+/-4 days (median 6 days, range, 4-14 days). Two of them received hormonal therapy [Gonadotropin Releasing Hormone (GnRH) analogue] postoperatively. At a follow-up of 14.16 patient-years (mean 2.83+/-1.08 years, range, 1.33-3.83 years) there was recurrence, 6.5 months postoperatively, in one patient that had not undergone closure of a tiny diaphragmatic hole and had not received hormonal treatment postoperatively. She was treated medically (amenorrhea for 6 months with GnRH analogue) and had no further recurrences (in 3.3 years).
Surgery is the treatment of choice of catamenial pneumothorax. It should aim to complete management of all lesions. The most common complication is recurrence. Early diagnosis and multidisciplinary treatment including hormonal therapy may be beneficial in high risk patients.
BJU Int. 2013 May;111(5):773-83. doi: 10.1111/j.1464-410X.2012.11673.x. Epub 2013 Jan 10.
Robot-assisted reconstructive surgery of the distal ureter: single institution experience in 16 patients.
WHAT’S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Open reconstructive surgery of the lower ureteric segment in adults often requires large incisions, as the basic prerequisite for such complex procedures is wide exposure. Published experience on minimally invasive techniques in this challenging surgical field, e.g. conventional laparoscopy or robot-assisted laparoscopy, still remains limited. We report our experience from one of the largest single institution series on robot-assisted reconstructive surgery of the distal ureter in adults, with a special focus on technical aspects of the different surgical procedures.
To describe the feasibility of and operative techniques used during different daVinci® robot-assisted laparoscopic reconstructive procedures of the distal ureter, and to report the short-term outcome of such procedures.
PATIENTS AND METHODS:
Between June 2009 and October 2011, 16 patients underwent robot-assisted operations of the distal ureter because of various underlying pathological conditions. We present a description of each procedure, the incidence of perioperative complications and the results of follow-up examination. The data were collected retrospectively using the patients’ records and questionnaires sent to the patients and the referring urologists. The follow-up examinations were done at the discretion of the referring urologists.
The surgical indications and operative techniques were as follows: seven distal ureteric resections [DUR] with psoas hitch procedures (+/- Boari flap; four), extravesical reimplantation (two) or end-to-end anastomosis (one) because of benign distal ureteric stricture; four DUR with psoas hitch procedure (+/- Boari flap) and pelvic lymphadenectomy for urothelial carcinoma of the ureter; one DUR with psoas hitch procedure and Boari flap because of unexpected locally recurrent prostate cancer; one extravesical reimplantation because of vesico-ureteric reflux; one bilateral intravesical reimplantation of ectopic ureters (as part of a radical prostatectomy); one resection of a non-functioning upper kidney pole with associated megaureter and ureterocele and intravesical reimplantation of lower pole ureter; one resection of pelvic endometriosis and ureterolysis with omental wrap. The median operative duration (including docking/undocking of the robot) was 260 min. There were no intraoperative complications but there was one conversion to open surgery. Complications according to the Clavien-Dindo classification occurred in 12 patients (75%) ≤ 90 days of surgery: 10 (62%) minor (grade I-II) and two (12%) major complications (grades IIIb and IVa, respectively). The median hospital stay after surgery was 7.5 days. At a median follow-up of 10.2 months, 15 patients (94%) remained without signs of urinary tract obstruction and 13 (81%) were asymptomatic.
Robot-assisted reconstructive surgery of the distal ureter is feasible and can be used without compromising the generally accepted principles of open surgical procedures. The functional outcome was good in short-term follow-up and severe postoperative complications were rare.
Diagn Interv Imaging. 2013 Mar;94(3):281-91. doi: 10.1016/j.diii.2012.11.003. Epub 2013 Jan 8.
Imaging of intestinal involvement in endometriosis.
Deep gastrointestinal involvement in endometriosis is characterised by fibrous, retractile thickening of the intestinal wall. The most common location is the upper rectum, in contiguity with a lesion of the torus uterinus. As part of a preoperative assessment, it is essential to establish an accurate and exhaustive map of intestinal lesions so that the surgeon can plan his actions. Transvaginal sonography and MRI correctly analyse pelvic and rectal involvement. Given the frequency of multiple intestinal sites, particularly sigmoid and associated ileo-caecal lesions, water enema CT should be performed. The role of rectal endoscopic sonography is debated.
Int J Mol Sci. 2013 Jan 10;14(1):1278-92. doi: 10.3390/ijms14011278.
ANRIL: molecular mechanisms and implications in human health.
ANRIL is a recently discovered long non-coding RNA encoded in the chromosome 9p21 region. This locus is a hotspot for disease-associated polymorphisms, and it has been consistently associated with cardiovascular disease, and more recently with several cancers, diabetes, glaucoma, endometriosis among other conditions. ANRIL has been shown to regulate its neighbor tumor suppressors CDKN2A/B by epigenetic mechanisms and thereby regulate cell proliferation and senescence. However, the clear role of ANRIL in the pathogenesis of these conditions is yet to be understood. Here, we review the recent findings on ANRIL molecular characterization and function, with a particular focus on its implications in human disease.
Int Urogynecol J. 2013 Jul;24(7):1083-4. doi: 10.1007/s00192-012-1995-5. Epub 2013 Jan 10.
A surgical case involving bladder endometriosis.
INTRODUCTION AND HYPOTHESIS:
The purpose is to demonstrate a surgical case of severe endometriosisinvolving a bladder endometriotic nodule.
This patient has a large 4-cm endometriotic nodule which obliterates the uterovesical pouch and invades the bladder. A video recording was made of the surgery involving a combined laparoscopic and transurethral approach to excise the endometriotic nodule together with partial cystectomy of the bladder. The surgery was carried out by two gynaecological laparoscopic surgeons and a urologist.
This video is a good demonstration of the multidisciplinary approach that is required for such a complex case. The surgery itself is technically difficult as the nodule is densely adherent to both bladder and uterus. This video was presented at the 2011 International Urogynecological Association 36th Annual Meeting in Portugal.
Endometriosis involving the urinary tract is rare and only occurs in approximately 1% of all patients with endometriosis (Schneider et al., Int J Urol 13:902-904, 2006). Surgery often involves a multidisciplinary approach and the surgery itself is technically challenging. This video is a good example of such a case.
Aesthetic Plast Surg. 2013 Feb;37(1):173-6. doi: 10.1007/s00266-012-0032-x. Epub 2013 Jan 10.
Unexpected encounter with painless endometriosis during abdominoplasty.
Subcutaneous endometriomas are cystic lesions that are rarely described. During the course of abdominoplasty surgery, a “surprise” encounter with a cyst containing brown material brought up the possibility that an atypical incarcerated hernia was entered. Dissection revealed no connection between the cyst and the rectus fascia and subsequent pathologic evaluation revealed an endometrioma. This report describes the unusual encounter with a painless endometrioma during abdominoplasty.
LEVEL OF EVIDENCE V:
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Rev Gastroenterol Peru. 2012 Oct-Dec;32(4):405-10.
Endometriosis of the ileum as cause intestinal obstruction.
We report the case of a patient of 40 years, in childbearing age with clinical abdominal obstruction, diagnostic laparoscopy revealed an ileal stenosing tumor, after intestinal resection their histopathological study found endometrial epithelium and stroma confirming the diagnosis of endometrial ileal endometriosis. It is the revision of this pathology. In young patients without previous surgery and with a history of painful periods bloating associated with defecation rhythm alteration, endometriosis should be included in the differential diagnosis of intestinal obstruction.
Rev Gastroenterol Peru. 2012 Oct-Dec;32(4):411-7.
Colorectal cancer endometriosis resembling stenosing extrapelvic: report of two cases.
We present two women of 40 and 42 years with colorectal endometriosis, both with a history of pelvic endometriosis and simultaneous episodes of rectal bleeding with menstruation. In endoscopic evaluations detected a sigmoid tumor and rectosigmoid tumor respectively, which apparently corresponds to stenosing colorectal cancer of epithelial origin.
Thorac Cardiovasc Surg. 2013 Jan;61(1):94-6. doi: 10.1055/s-0032-1330227. Epub 2013 Jan 10.
Successful treatment of catamenial hemoptysis by video-assisted thoracoscopic surgery.
We report a case of a 23-year-old woman with a 5-year history of recurrent hemoptysis during menstrual period. Catamenial hemoptysis was diagnosed using chest computed tomography and bronchoscopic examination during menstruation. The patient was managed successfully with wedge resection and has been free of recurrence for 5 years. We suggest that surgery is an effective treatment, and complete resection with accurate localization is important for the prevention of recurrence.
Surg Today. 2014 Apr;44(4):767-72. doi: 10.1007/s00595-012-0459-3. Epub 2013 Jan 12.
Surgical scar endometriosis.
Endometriosis is a common disorder in females of reproductive age. Surgical scar endometrioma after cesarean section develops in 1-2% of patients, and usually presents as a tender and painful abdominal wall mass. The diagnosis is suggested by pre or perimenstrual pelvic pain and is often established only by histology. In this retrospective observational cohort study, we reviewed the medical records of five patients with a histopathological diagnosis of scar endometriosis. A scar mass was found on a previous Pfannenstiel incision in four patients and in a median cesarean section in one patient. The mean age at diagnosis (38.6 years, median 38) was older than reported elsewhere. A histological examination of the surgical specimen confirmed the diagnosis of endometriosisin all cases. During the follow-up period (mean 34.6 months), local recurrence (n = 1) and pelvic recurrence (n = 1) were treated surgically. Surgery is the treatment of choice for surgical scar endometriosis. Excision with histologically proven free surgical margins of 1 cm is mandatory to prevent recurrence. As scar endometriosis may be associated with pelvic localization, explorative abdominal laparoscopy may be indicated to exclude the intraperitoneal spread of the disease in symptomatic patients.
Zhongguo Zhong Yao Za Zhi. 2012 Oct;37(20):3122-5.
Magnetic resonance characteristics of endometriosis rat model.
To establish a non-invasive, repeatable and dynamic study method in endometriosis rat model using magnetic resonance imaging (MRI), in order to explore the magnetic resonance characteristics of the model.
Endometrium tissues were transplanted into left abdominal walls of unmated adult female SD rats. After surgery, pathological changes were observed and MRI scanning was made for the ectopic lesions.
The endometriosis rat model was successfully established and the ectopic lesions imaged strong hyperintense on DWI, hypointense on T1WI, hyperintense on T2WI with a clear border, without enhancement on CE-T1 WI.
The lesions can be clearly observed in the MRI images on the endometriosis rat model established by this method, which facilitates repeat experiments and continuous observation studies.
Vojnosanit Pregl. 2012 Nov;69(11):1013-6.
Acute small bowel obstruction due to ileal endometriosis: a case report and review of the most recent literature.
Endometriosis is defined as the presence of benign endometrial glands and stroma outside the normal anatomical location. Endometriosis of the small bowel, especially symptomatic small bowel involvement, is very unusual.
We presented a 45-year-old woman with acute intestinal obstruction due to ileal endometriosisThe patient complained of severe abdominal pain, nausea and vomitting. Immediate laparotomy was carried out. Above the ileocecal valve there was an ulcerated, edematous and fragile segmental lesion that caused intestinal obstruction. Histology of this ileal segment revealed endometriosis and an annular stricture that again showed foci of endometriosis.
In reproductive-age women with the symptoms of intestinal obstruction, intestinal endometriosisshould be kept in mind.
Fertil Steril. 2013 Apr;99(5):1346-1355.e5. doi: 10.1016/j.fertnstert.2012.11.055. Epub 2013 Jan 8.
MicroRNA miR-145 inhibits proliferation, invasiveness, and stem cell phenotype of an in vitro endometriosis model by targeting multiple cytoskeletal elements and pluripotency factors.
To study the function of miR-145, known to be dysregulated in endometriosis, and to identify its target genes in an in vitro endometriosis model.
Experimental laboratory study.
University medical centers.
Primary endometrial stroma cells were derived from eutopic endometrium of three American Society for Reproductive Medicine stage III endometriosis patients and from ectopic lesions of four patients with deep infiltrating endometriosis.
The human endometriotic cell line 12Z and primary eutopic and ectopic endometrial stroma cells were transiently transfected with miR-145 precursors or anti-miR-145 inhibitors and investigated for posttranscriptional regulation of predicted target genes and changes in cell behavior.
MAIN OUTCOME MEASURE(S):
Predicted target expression was measured by quantitative reverse transcription-polymerase chain reaction and Western blotting, and altered cell behavior was monitored by cell proliferation assays. The 12Z cells were additionally investigated by Matrigel invasion assays, cell cycle analysis, side population analysis, and aldehyde dehydrogenase activity assays.
In all cells investigated, miR-145 overexpression inhibited cell proliferation and induced down-regulation of FASCIN-1, SOX2, and MSI2. In 12Z cells miR-145 upregulation increased Matrigel invasiveness and reduced side population and aldehyde dehydrogenase-1 activity. Additional down-regulated targets in 12Z cells included OCT4, KLF4, PODXL, JAM-A, and SERPINE1/PAI-1. ACTG2 and TAGLN were up-regulated upon pre-miR-145 transfection. JAM-A, FASCIN-1, and PAI-I down-regulation in 12Z cells were confirmed by Western blotting.
miR-145 inhibits endometriotic cell proliferation, invasiveness, and stemness by targeting multiple pluripotency factors, cytoskeletal elements, and protease inhibitors.
J Minim Invasive Gynecol. 2013 Jan-Feb;20(1):100-3. doi: 10.1016/j.jmig.2012.09.012
Retrocervical deep infiltrating endometriotic lesions larger than thirty millimeters are associated with an increased rate of ureteral involvement.
To estimate the presence of ureteral involvement in deep infiltrating endometriosis (DIE) affecting the retrocervical area.
Retrospective study of women undergoing laparoscopic treatment of DIE affecting the retrocervical area.
Canadian Task Force classification II-3.
Tertiary referral private hospital.
We evaluated 118 women who underwent laparoscopy for the treatment of retrocervical DIE lesions between January 2010 and March 2012.
All women underwent laparoscopic surgery for the complete treatment of DIE. After surgery all specimens were sent for pathologic examination to confirm the presence of endometriosis.
Patients with pathologically-confirmed retrocervical DIE were divided into 2 groups according to the size of the lesion (group 1: lesions ≥ 30 mm; group 2: lesions < 30 mm) and the rate of ureteral endometriosis was compared between both groups.
Ureteral involvement was present in 17.9% (95% confidence interval [CI] 10%-29.9%) of women with retrocervical lesions ≥ 30 mm whereas in only 1.6% (95% CI 0.4%-8.5%) of those with lesions <30 mm (odds ratio = 13.3 [95% CI 1.6-107.3]).
Patients undergoing surgery for retrocervical DIE lesions ≥ 30 mm in diameter have a greater risk of having ureteral involvement (17.9%).
Int J Gynecol Cancer. 2013 Feb;23(2):244-8. doi: 10.1097/IGC.0b013e31827aa0bb.
Long term survival of ovarian endometriosis associated clear cell and endometrioid ovarian cancers.
This study aimed to analyze long-term survival of clear cells (CCs) and endometrioid (E) ovarian cancer cases according to presence of endometriosis in the pathologic report.
This is a retrospective analysis of 47 CC and 66 E ovarian cancer cases observed consecutively at our center between 1990 and 2010.All cases had first surgery at our center or were referred to it for treatment and follow-up.Cases were identified according to the original diagnosis reported in clinical records.All pathologic reports were reviewed, and cases were classified with or without pathologic evidence of endometriosis on the basis of the pathologic report.Follow-up was updated in March 2011. The follow-up median was 147 months (range, 116-171).
Endometriosis-associated ovarian cancer cases were more frequently diagnosed at stage I to II than cases without endometriosis: among the 36 endometriosis-associated ovarian cancer cases, 25 (69%) were at stage I or II, and the corresponding value was 35 (46%) of 77 among cases without endometriosis (P = 0.0173).The presence of endometriosis tended to be associated with a higher 10-year survival rate: after taking the potential confounding effect of stage into account, the finding was not statistically significant (hazards ratio, 0.7; 95% confidence interval, 0.3-1.5).
This analysis shows that EA CCs and E ovarian cases are diagnosed at an earlier stage than cases without endometriosis. No clear association emerged between presence of endometriosis and survival.
Reprod Sci. 2013 Sep;20(9):1030-7. doi: 10.1177/1933719112472736. Epub 2013 Jan 11.
Müllerianosis: four developmental (embryonic) mullerian diseases.
The theory of müllerianosis predicts that embryonic müllerian tissue, misplaced during organogenesis, results in the formation of 4 benign müllerian diseases-developmental adenomyosis, endometriosis, endosalpingiosis, and endocervicosis-(developmental müllerian diseases) that will be identified in human female fetuses, infants, children, adolescents, and adults. Direct evidence is presented to support the existence of developmental adenomyosis, developmental endometriosis, and developmental endocervicosis in human female fetuses along with strong circumstantial evidence supporting the existence of all 4 developmental müllerian diseases in human female infants, children, adolescents, and adults. This evidence throws light upon the pathogenesis of rare müllerian lesions whose pathogenesis remains inexplicable by classical and modern theories. Furthermore, this research has scientific and clinical relevance: scientific relevance because it opens up a new field of comparative research-the 4 developmental müllerian diseases complement the 4 acquired müllerian diseases; clinical relevance because it identifies rare müllerian diseases curable by complete surgical excision.
Hum Reprod. 2013 May;28(5):1406-17. doi: 10.1093/humrep/des466. Epub 2013 Jan 12.
Reproductive characteristics in relation to ovarian cancer risk by histologic pathways.
Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based classification?
Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer.
WHAT IS KNOWN ALREADY:
Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways.
This case-control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers’ license and town resident lists and were frequency matched with the cases based on age and study center.
MAIN RESULTS AND THE ROLE OF CHANCE:
We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR = 1.92, 95% CI: 1.36-2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥ 3 versus 0 children, OR = 0.15, 95% CI: 0.11-0.21), having a previous tubal ligation (OR = 0.40, 95% CI: 0.26-0.60) and more weakly hysterectomy (OR = 0.71, 95% CI: 0.45-1.13). In analyses of histologic pathways, parity (≥ 3 versus 0 children, OR = 0.13, 95% CI: 0.10-0.18) and having a previous tubal ligation (OR = 0.41, 95% CI: 0.28-0.60) or hysterectomy (OR = 0.54, 95% CI: 0.34-0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR = 2.41, 95% CI: 1.78-3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility.
LIMITATIONS, REASONS FOR CAUTION:
A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study.
WIDER IMPLICATIONS OF THE FINDINGS:
This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types.
STUDY FUNDING/COMPETING INTEREST(S):
This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare.
Hum Reprod. 2013 Mar;28(3):835-9. doi: 10.1093/humrep/des457. Epub 2013 Jan 12.
Replication of endometriosis-associated single-nucleotide polymorphisms from genome-wide association studies in a Caucasian population.
Is it possible to replicate the previously identified genetic association of four single-nucleotide polymorphisms (SNPs), rs12700667, rs7798431, rs1250248 and rs7521902, with endometriosis in a Caucasian population?
A borderline association was observed for rs1250248 and endometriosis (P = 0.049). However, we could not replicate the other previously identified endometriosis-associated SNPs (rs12700667, rs7798431 and rs7521902) in the same population.
WHAT IS KNOWN ALREADY:
Endometriosis is considered a complex disease, influenced by several genetic and environmental factors, as well as interactions between them. Previous studies have found genetic associations with endometriosis for SNPs at the 7p15 and 2q35 loci in a Caucasian population.
STUDY DESIGN, SIZE, DURATION:
Allele frequencies of SNPs were investigated in patients with endometriosisand controls.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Blood samples and peritoneal biopsies were taken from a Caucasian female population consisting of 1129 patients with endometriosis and 831 controls. DNA was extracted for genotyping. The study was performed at a University hospital and research laboratories.
MAIN RESULTS AND THE ROLE OF CHANCE:
A weak association with endometriosis (all stages) was observed for rs1250248 (P = 0.049). No significant associations were observed for the SNPs rs12700667, rs7798431 and rs7521902. A non-significant trend towards the association of rs1250248 with moderate/severe endometriosis was observed (odds ratio 1.18, 95% confidence interval 0.97-1.44).
LIMITATIONS, REASONS FOR CAUTION:
The inability to confirm all previous findings may result from differences between populations and type II errors.
WIDER IMPLICATIONS OF THE FINDINGS:
Our result demonstrates the difficulty of identifying common genetic variants in complex diseases.
STUDY FUNDING/COMPETING INTEREST(S):
This study was supported by grants from the Karolinska Institutet and Stockholm City County/Karolinska Institutet (ALF), Stockholm, Sweden, Swedish Medical Research Council (K2007-54X-14212-06-3, K2010-54X-14212-09-3), Stockholm, Sweden, Leuven University Research Council (Onderzoeksraad KU Leuven), the Leuven University Hospitals Clinical Research Foundation (Klinisch onderzoeksfonds) and by the National Scientific Foundation (Fonds voor Wetenschappelijk Onderzoek, FWO). The authors have no conflict of interest.
Z Gastroenterol. 2013 Jan;51(1):32-6. doi: 10.1055/s-0032-1325329. Epub 2013 Jan 11.
A very rare submucosal tumour of the rectum – primary endometrioid adenocarcinoma of the rectum wall.
A 56-year-old female, with a past history of hysterectomy 13 years previously due to uterine myomata, presented with complaints of pain around the anus of a few months duration. Three years previously she underwent a colonoscopy, which was found to be unremarkable. A high suspicion of a submucosal tumour of the rectum in endoscopic examinations was confirmed by endoscopic ultrasound. The biopsy could not specify the tumour characteristics. Based on the diagnosis of a 4 cm submucosal tumour with infiltration of bowel wall and regional lymph nodes the affected segment was resected. Histolopathology revealed an adenocarcinoma involving tissue from the outer bowel wall to the submucosa. However, immunohistochemistry revealed an endometrioid adenocarcinoma, suspicious for primary endometrioid adenocarcinoma of the ovary with rectum metastasis in the absence of a uterus. But this assumption could not be confirmed in the excised ovary. The tumour cells were immunopositive for cytokeratin 7, CA 12 - 5, vimentin and oestrogen receptor, but negative for cytokeratin 20 and CDX-2. Ultimately, we report a very rare case of primary endometrioid adenocarcinoma arising in endometriosis in the rectum wall and presenting as a submucosal tumour.