Vestn Rentgenol Radiol. 2014 May-Jun;(3):24-34.
Capabilities of magnetic resonance imaging to diagnose infiltrating pelvic endometriosis.
Deep infiltrating endometriosis is a disease in reproductive-aged women, resulting in varying chronic pelvic pains and infertility, which requires surgical treatment. Objective–to determine the capabilities of magnetic resonance imaging (MRI) to diagnose pelvic endometriosis and to elaborate an optimal scanning protocol if this disease is suspected. Small pelvic MRI has a high accuracy in the diagnosis of endometriosis and can visualize most endometrioid implants, including those that are located under adhesions and in the subperitoneal regions. Just the same, a radiodiagnostician should not forget that MRI is of low informative value in identifying bowel endometriosis. Hence, when diagnosing deep infiltrating endometriosis, MRI should be complemented with transvaginal ultrasonography to detect endometrioid implants on the bowel walls as the informative value in this aspect is above.
BMC Womens Health. 2015;15:13.
Endometriosis node in gynaecologic scars: a study of 17 patients and the diagnostic considerations in clinical experience in tertiary care center.
Endometriosis nodes are observed in extra pelvic locations, particularly in gynaecological scars, with the abdominal wall being one of the most frequent locations. The main objective of the study is to review patient characteristics of cases of endometriosis nodes in gynaecological scars.
A retrospective, observational and descriptive study with a cohort of patients from Hospital 12 de Octubre was conducted from January 2000 to January 2012. We analysed all of the patients who presented with an endometriosis node in a gynaecological scar presentation who had undergone surgery in that period. Descriptive data were collected and analysed.
A total of 17 patients with an anatomopathological diagnosis of an endometriosis node in a gynaecological scar were found. The following variables were studied: the age at diagnosis (32.5 years +/- 5.5 years), personal and obstetric history, time from surgery to diagnosis (4.2 years +/- 3.4 years), symptoms (a painful mass that grows during menstruation is the most frequent symptom in our patients), technical analyses by computed tomography (CT), magnetic resonance (MR) or fine needle aspiration (FNA) (77% of the patients), node size (2.5 cm +/- 1.1 cm) and location (caesarean scar, 82%; episiotomy scar, 11.7%; and laparoscopic surgery port, 5.8%), involvement of adjacent structures (29% of the patients), treatment (exeresis with a security margin in all the patients) and other endometriosis locations (14% of the patients).
A high level of suspicion is required to diagnose gynaecological scar endometriosis, which should be suspected in the differential diagnosis of scar masses in reproductive-aged women. Several theories have been proposed to explain the formation of endometriosis nodes in extrauterine localizations. The two of them that seem to be more plausible are the metaplasia and transport theories. Imaging with ultrasound, CT and MR facilitate the diagnosis. FNA could be used for preoperative diagnosis. Treatment must be by node resection with a security margin. In some cases, surgery could be combined with hormonal treatment.
Int J Clin Exp Med. 2015 Jan 15;8(1):1059-65
Hydronephrosis due to ureteral endometriosis in women of reproductive age.
The aim of the present study was to improve the understanding of ureteral endometriosis, and remind the clinics to be highly suspicious of it in women of reproductive age with hydronephrosis without evidence of stones and malignancy.
A retrospective analysis was performed on a database of 82 patients who underwent surgery for hydronephrosis due to ureteral endometriosis between Jan. 2007 and Apr. 2014.
All patients evaluated in this study were divided into three groups: Group A consisted of patients between 20-30 years (n = 12), Group B comprised of patients between 31-40 years (n = 29), Group C consisted of patients between 41-50 years (n = 41). Patients in Group C had a greater prevalence of pelvic pain compared with patients in Group A and Group B (P < 0.05). However there were no differences with respect to the prevalence of other non-specific genitourinary symptoms and the urinary symptoms. Infertility was found to occur more frequently in patients in Group A compared with patients in Group B and Group C (P < 0.05). Because of the lack of specific symptoms, ureteral endometriosis was diagnosed (20.1 ± 10.3) months on average after the patients suffered from mild hydronephrosis or mild loin pain. Preoperative examinations showed different degree of hydronephrosis, but lack of specificity. All patients underwent surgery by laparotomy or laparoscopy, such as ureterectomy with ureteroureterostomy or ureterocystoneostomy. The pathological examination confirmed the diagnosis of ureteral endometriosis.
The diagnosis of ureteral endometriosis is elusive and relies heavily on clinical suspicion. Hence, women in the reproductive age, especially with infertility and pelvic pain, who have hydronephrosis without evidence of stones and malignance, should be adequately assessed via imaging techniques or diagnostic laparoscopy or cystoscopy to highly suspect the diagnosis of ureteral endometriosis.
Biomed Res Int. 2015;2015:450468
Inhibition of adhesion, proliferation, and invasion of primary endometriosisand endometrial stromal and ovarian carcinoma cells by a nonhyaluronan adhesion barrier gel.
Endometriosis is a chronic disease of women in the reproductive age, defined as endometrial cells growing outside of the uterine cavity and associated with relapses. Relapses are hypothesized to correlate with incomplete surgical excision or result from nonrandom implantation of new endometrial implants in adjacent peritoneum. Thus, surgical excision could lead to free endometriotic cells or tissue residues, which readhere, grow, and invade into recurrent lesions. Barrier agents are frequently used to prevent postoperative adhesions. We tested if the absorbable cell adhesion barrier gel Intercoat consisting of polyethylene oxide and sodium carboxymethyl cellulose could inhibit cellular adhesion, proliferation, and invasion of primary endometriosis and endometrial cells. Due to an association of endometriosis with ovarian carcinoma, we tested two ovarian carcinoma cell lines. Prior to cell seeding, a drop of the barrier gel was placed in cell culture wells in order to test inhibition of adherence and proliferation or coated over a polymerized collagen gel to assay for prevention of invasion. Results showed that the barrier gel significantly inhibited cell adherence, proliferation, and invasion of endometriosis and endometrial stromal cells as well as ovarian carcinoma cells in culture. Our findings could help to prevent local cell growth/invasion and possible consequent recurrences.
J Surg Case Rep. 2015 Mar 18;2015(3).
Endometrioma in a virgin abdomen masquerading as an intramuscular lipoma.
Endometriosis is the presence of endometrial tissue outside the uterine cavity. It has been previously reported in the abdominal wall secondary to gynaecological surgery. We present the case of a 32-year woman with endometrioma of the abdominal wall masquerading as an intramuscular lipoma with no previous surgical history.
J Surg Case Rep. 2015 Mar 18;2015(3).
Primary umbilical endometriosis: a cause of a painful umbilical nodule.
A female patient presented with a painful swelling in the umbilicus. Ultrasonography demonstrated a hypodense nodule of 1.8 cm. Surgical exploration revealed a subcutaneous, dark discoloured, lobulated swelling at the bottom of the umbilicus, which turned out to be primary umbilical endometriosis (PUE). Primary umbilical endometriosis is a rare and benign disorder, caused by the presence of ectopic endometrial tissue in the umbilicus, which can present as a painful, discoloured swelling in the umbilicus. The clinical distinction between primary umbilical endometrioses and other causes of an umbilical nodule is difficult. Additional imaging modalities do not show any pathognomonic signs for establishing this diagnose. Surgical exploration and excision are a safe and definitive treatment of primary umbilical endometrioses. This case highlights the importance of including PUE in the differential diagnosis of women with a painful umbilical nodule.
J UOEH. 2015 Mar 1;37(1):17-22.
Pregnancy after hysteroscopic metroplasty under laparoscopy in a woman with complete septate uterus: a case report.
A 31-year-old nulligravid woman with a 3 year history of infertility visited our hospital. After consultation and a transvaginal ultrasound and MR imaging, her uterine anomaly was identified as complete septate uterus: class V (a) by the American Fertility Society (AFS). She had a doubled uterine cervix and a vaginal septum. Hysteroscopic metroplasty was performed with the aid of a laparoscopy. Both tubal patencies were confirmed with indigocarmine in a laparoscopic image. Laparoscopic electronic cautery was also done on the left ovarian endometrioma (stage 1 endometriosis; the revised American Society for Reproductive Medicine (rASRM) classification 4 point minimal). We distrained an intrauterine device in the uterine cavity and removed it after two cycles of menstruation. The patient subsequently became pregnant during her third menstrual cycle and the current progress of her pregnancy is favorable.
Hum Reprod. 2015 May;30(5):1263-75.
Functional evaluation of genetic variants associated with endometriosis near GREB1.
Do DNA variants in the growth regulation by estrogen in breast cancer 1 (GREB1) region regulate endometrial GREB1 expression and increase the risk of developing endometriosis in women?
We identified new single nucleotide polymorphisms (SNPs) with strong association with endometriosis at the GREB1 locus although we did not detect altered GREB1 expression in endometriosispatients with defined genotypes.
WHAT IS ALREADY KNOWN:
Genome-wide association studies have identified the GREB1 region on chromosome 2p25.1 for increasing endometriosis risk. The differential expression of GREB1 has also been reported by others in association with endometriosis disease phenotype.
STUDY DESIGN, SIZE, DURATION:
Fine mapping studies comprehensively evaluated SNPs within the GREB1 region in a large-scale data set (>2500 cases and >4000 controls). Publicly available bioinformatics tools were employed to functionally annotate SNPs showing the strongest association signal with endometriosis risk. Endometrial GREB1 mRNA and protein expression was studied with respect to phases of the menstrual cycle (n = 2-45 per cycle stage) and expression quantitative trait loci (eQTL) analysis for significant SNPs were undertaken for GREB1 [mRNA (n = 94) and protein (n = 44) in endometrium].
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Participants in this study are females who provided blood and/or endometrial tissue samples in a hospital setting. The key SNPs were genotyped using Sequenom MassARRAY. The functional roles and regulatory annotations for identified SNPs are predicted by various publicly available bioinformatics tools. Endometrial GREB1 expression work employed qRT-PCR, western blotting and immunohistochemistry studies.
MAIN RESULTS AND THE ROLE OF CHANCE:
Fine mapping results identified a number of SNPs showing stronger association (0.004 < P < 0.032) with endometriosis risk than the original GWAS SNP (rs13394619) (P = 0.034). Some of these SNPs were predicted to have functional roles, for example, interaction with transcription factor motifs. The haplotype (a combination of alleles) formed by the risk alleles from two common SNPs showed significant association (P = 0.026) with endometriosis and epistasis analysis showed no evidence for interaction between the two SNPs, suggesting an additive effect of SNPs on endometriosis risk. In normal human endometrium, GREB1 protein expression was altered depending on the cycle stage (significantly different in late proliferative versus late secretory, P < 0.05) and cell type (glandular epithelium, not stromal cells). However, GREB1 expression in endometriosis cases versus controls and eQTL analyses did not reveal any significant changes.
LIMITATIONS, REASONS FOR CAUTION:
In silico prediction tools are generally based on cell lines different to our tissue and disease of interest. Functional annotations drawn from these analyses should be considered with this limitation in mind. We identified cell-specific and hormone-specific changes in GREB1 protein expression. The lack of a significant difference observed following our GREB1 expression studies may be the result of moderate power on mixed cell populations in the endometrial tissue samples.
WIDER IMPLICATIONS OF THE FINDINGS:
This study further implicates the GREB1 region on chromosome 2p25.1 and the GREB1 gene with involvement in endometriosis risk. More detailed functional studies are required to determine the role of the novel GREB1 transcripts in endometriosis pathophysiology.
STUDY FUNDING/COMPETING INTERESTS:
Funding for this work was provided by NHMRC Project Grants APP1012245, APP1026033, APP1049472 and APP1046880. There are no competing interests.
Hum Reprod. 2015 May;30(5):1079-88
Low-dose human menopausal gonadotrophin versus clomiphene citrate in subfertile couples treated with intrauterine insemination: a randomized controlled trial.
Can controlled ovarian stimulation with low-dose human menopausal gonadotrophin (hMG) improve the clinical pregnancy rate when compared with ovarian stimulation with clomiphene citrate (CC) in an intrauterine insemination (IUI) programme for subfertile couples?
Ovarian stimulation with low-dose hMG is superior to CC in IUI cycles with respect to clinical pregnancy rate.
WHAT IS KNOWN ALREADY:
IUI after ovarian stimulation is an effective treatment for mild male subfertility, unexplained subfertility and minimal-mild endometriosis, but it is unclear which medication for ovarian stimulation is more effective.
STUDY DESIGN, SIZE, DURATION:
A total of 330 women scheduled for IUI during 657 cycles (September 2004-December 2011) were enrolled in an open-label randomized clinical trial to ovarian stimulation with low-dose hMG subcutaneous (n = 334, 37.5-75 IU per day) or CC per oral (n = 323, 50 mg/day from Day 3-7). Assuming a difference of 10% in ‘clinical pregnancy with positive fetal heart beat’, we needed 219 cycles per group (alpha-error 0.05, power 0.80).
PARTICIPANTS/MATERIALS, SETTING, METHODS:
We studied subfertile couples with mild male subfertility, unexplained subfertility or minimal-mild endometriosis. Further inclusion criteria were failure to conceive for ≥12 months, female age ≤42 years, at least one patent Fallopian tube and a total motility count (TMC) ≥5.0 million spermatozoa after capacitation. The primary end-point was clinical pregnancy. Analysis was by intention to treat and controlled for the presence of multiple measures, as one couple could have more randomizations in multiple cycles. Linear mixed models were used for continuous measures. For binary outcomes we estimated the relative risk using a Poisson model with log link and using generalized estimating equations.
MAIN RESULTS AND THE ROLE OF CHANCE:
When compared with ovarian stimulation with CC, hMG stimulation was characterized by a higher clinical pregnancy rate (hMG 48/334 (14.4%) versus CC 29/323 (9.0%), relative risk (RR) 1.6 (95% confidence interval (CI) 1.1-2.4)), higher live birth rate (hMG 46/334 (13.8%) versus CC 28/323 (8.7%), RR 1.6 (95% CI 1.0-2.4)), low and comparable multiple live birth rate (hMG 3/46 (6.5%) versus CC 1/28 (3.6%), P > 0.99), lower number of preovulatory follicles (hMG 1.2 versus CC 1.5, P < 0.001), increased endometrial thickness (hMG 8.5 mm versus CC 7.5 mm, P < 0.001), and a lower cancellation rate per started cycle (hMG 15/322 (4.7%) versus CC 46/298 (15.4%), P < 0.001).
LIMITATIONS, REASONS FOR CAUTION:
We randomized patients at a cycle level, and not at a strategy over multiple cycles.
WIDER IMPLICATIONS OF THE FINDINGS:
This study showed better reproductive outcome after ovarian stimulation with low-dose gonadotrophins. A health economic analysis of our data is planned to test the hypothesis that ovarian stimulation with low-dose hMG combined with IUI is associated with increased cost-effectiveness when compared with ovarian stimulation with CC.
STUDY FUNDING/ COMPETING INTERESTS:
T.M.D. and K.P. were supported by the Clinical Research Foundation of UZ Leuven, Belgium. This study was also supported by the Ferring company (Copenhagen, Denmark) which provide free medication (Menopur) required for the group of patients who were randomized in the hMG COS group. The Ferring company was not involved in the study design, data analysis, writing and submission of the paper.
JSLS. 2015 Jan-Mar;19(1)
Feasibility and safety of outpatient total laparoscopic hysterectomy.
BACKGROUND AND OBJECTIVE:
Ambulatory total laparoscopic hysterectomy (TLH) could lead to significant cost savings, but some fear the effects of what could be premature postsurgical discharge. We sought to estimate the feasibility and safety of TLH as an outpatient procedure for benign gynecologic conditions.
We report a prospective, consecutive case series of 128 outpatient TLHs performed for benign gynecologic conditions in a tertiary care center.
Of the 295 women scheduled for a TLH, 151 (51%) were attempted as an outpatient procedure. A total of 128 women (85%) were actually discharged home the day of their surgery. The most common reasons for admission the same day were urinary retention (19%) and nausea (15%). Indications for hysterectomy were mainly leiomyomas (62%), menorrhagia (24%), and pelvic pain (9%). Endometriosis and adhesions were found in 23% and 25% of the cases, respectively. Mean estimated blood loss was 56 mL and mean uterus weight was 215 g, with the heaviest uterus weighing 841 g. Unplanned consultation and readmission were infrequent, occurring in 3.1% and 0.8% of cases, respectively, in the first 72 hours. At 3 months, unplanned consultation, complication, and readmission had occurred in a similar proportion of inpatient and outpatient TLHs (17.2%, 12.5%, and 4.7% versus 18.1%, 12.7%, and 5.4%, respectively). In a logistic regression model, uterus weight, presence of adhesions or endometriosis, and duration of the operation were not associated with adverse outcomes.
Same-day discharge is a feasible and safe option for carefully selected patients who undergo an uncomplicated TLH, even in the presence of leiomyomas, severe adhesions, or endometriosis.
Anesth Pain Med. 2015 Feb 1;5(1):e22372.
The effect of gabapentin on reducing pain after laparoscopic gastric bypass surgery in patients with morbid obesity: a randomized clinical trial.
Pain after laparoscopic gastric bypass surgery (LGBP) is a major problem. Gabapentin is an anticonvulsant drug that can be effective in postoperative pain control.
This study examined the effect of preoperative administration of gabapentin on reducing pain after LGBP in patients with morbid obesity.
PATIENTS AND METHODS:
This randomized clinical trial was performed in Hazrat Rasoul Akram Medical Center in Tehran. A total of 60 patients undergoing LGBP were randomly allocated into two groups; one group received 100 mg of oral gabapentin and the other group received placebo. Pain was evaluated at recovery time, and at the first, second, fourth and sixth hour of surgery by visual analog scale. The number and dose of opioid use after surgery and incidence of postoperative complications, such as nausea and vomiting, agitation, and headache, were also recorded.
The mean pain score in the group receiving gabapentin was significantly lower than the placebo group (P < 0.001). Indications and dose of opioid consumption between the two groups were not statistically significant. Incidence of nausea/vomiting (P = 0.028) as well as agitation (P = 0.037) was significantly lower in the gabapentin group.
Administration of gabapentin before surgery can reduce pain after LGBP. Furthermore, it is not accompanied by significant short-term adverse effects.
Neuro Endocrinol Lett. 2015;36(1):15-23.
Neuroendocrine and stress-related aspects of endometriosis.
Endometriosis is a model of a benign gynecologic disease associated with two major symptoms: pain and infertility. When becomes chronic, severe psychological and neuroendocrine changes may occur. The high levels of perceived stress caused by symptoms cause a neuroendocrine disequilibrium thus contributing to the progression of the disease. Elevated stress levels alter hormonal secretions, mood and behavior, sexual disorders and appetite custom. Inflammatory comorbidities may be associated with elevated stress in endometriotic patients (inflammatory bowel disease, fibromyalgia, chronic fatigue) and even autoimmune diseases (thyroid disease, systemic lupus erythematosus, multiple sclerosis). Neurogenic mechanisms are described in endometriotic lesions and they affect peripheral and central nervous system of these patients increasing pain sensitivity and stress reactivity. In conclusion, endometriosis is a disease which affects reproductive and neuroendocrine functions with a great impact on women’s health and quality of life.
Arab J Gastroenterol. 2015 Mar;16(1):33-5.
Colonic obstruction caused by endometriosis solved with a colonic stent as a bridge to surgery.
Self-expanding metal stents are an established treatment for malignant colon strictures, either as palliative treatment or as a bridge to later surgery. Little data exist regarding the use of stents for benign obstructions and the rate of subsequent complications related to the procedure is high. After reviewing the existing literature, we found only one case of stent placement in an intestinal obstruction caused by endometriosis, as a bridge to surgery. The use of prostheses in benign disease has a higher rate of complications such as stent migration and gut perforation. Such complications are even more likely to happen when the stent has been placed as a bridge to surgery and it is delayed for more than 7 days. This is the case of a young woman presenting an acute intestinal obstruction related to endometrioma. Stent placement was used in this case as a bridge to surgery with successful results.
Eur J Obstet Gynecol Reprod Biol. 2015 May;188:70-3.
Impact of osteopathic manipulative therapy on quality of life of patients with deep infiltrating endometriosis with colorectal involvement: results of a pilot study.
A prospective pilot study to evaluate the potential role of osteopathic manipulative therapy (OMT) on quality of life (QOL) of patients with Deep Infiltrating Endometriosis (DIE) and colorectal involvement.
Twenty patients with DIE and colorectal infiltration completed the SF-36 QOL questionnaire before and after undergoing OMT.
The median age (range) of the patients was 30.4 years (22-39). Thirty-five percent of the patients had undergone previous surgery for endometriosis and 70% were on medical treatment. Fifteen of the 20 patients (75%) completed the protocol. There was no difference in the epidemiological characteristics or in the pre-OMT Physical Component Summary (PCS) and Mental Component Summary (MCS) of the SF-36 questionnaire between patients who completed the protocol or not. After a mean period of 24 days (15-53), a significant improvement in PCS (p=0.03) and MCS (p=0.0009) compared to pre-OMT values was observed giving a success rate of 80% and 60% in intention-to-treat, respectively.
Our results support that OMT can improve QOL of patients with DIE and colorectal involvement. Moreover, this pilot study can serve to determine power calculations for future randomized trials.
J Mol Diagn. 2015 May;17(3):325-34.
Panels of cytokines and other secretory proteins as potential biomarkers of ovarian endometriosis.
Endometriosis is a gynecologic disease that is characterized by nonspecific symptoms and invasive diagnostics. To date, there is no adequate noninvasive method for the diagnosis of endometriosis. Although more than 100 potential biomarkers have been investigated in blood and/or peritoneal fluid, none of these has proven useful in clinical practice. The aim to find a suitable panel of biomarkers that would allow noninvasive diagnosis thus remains of interest. We evaluated the concentrations of 16 cytokines and other secretory proteins in serum and peritoneal fluid of 58 women with ovarian endometriosis (cases) and 40 healthy women undergoing sterilization or patients with benign ovarian cysts (controls) using multiplexed double fluorescence-based immunometric assay platform and enzyme-linked immunosorbent assay. Significantly higher concentrations of glycodelin-A were shown in serum, and significantly higher levels of glycodelin-A, IL-6, and IL-8, and lower levels of leptin were measured in the peritoneal fluid of cases versus controls. In serum, the best performance was shown by models that included the ratio of leptin/glycodelin-A and the ratio of ficolin 2/glycodelin-A, whereas in the peritoneal fluid the best models included the ratio of biglycan/leptin, regulated on activation normal T-cell expressed and secreted/IL-6 and ficolin-2/glycodelin-A, and IL-8 per milligram of total protein, all in combination with age. The models using serum and peritoneal fluid distinguished between ovarian endometriosis patients and controls regardless of the menstrual cycle phase with relatively high sensitivity (72.5% to 84.2%), specificity (78.4% to 91.2%), and area under the curve (0.85 to 0.90).
Post Reprod Health. 2015 Mar;21(1):16-23.
Minimising menopausal side effects whilst treating endometriosis and fibroids.
Medical management of endometriosis and fibroids involves manipulation of the hypothalamic-pituitary-gonadal axis to alter the balance of sex hormones thereby inhibiting disease progression and ameliorate symptoms. Unfortunately, resultant menopausal symptoms sometimes limit the tolerability and duration of such treatment. The use of gonadotrophin-releasing hormone agonists to treat these diseases can result in short-term hypoestrogenic and vasomotor side effects as well as long-term impacts on bone health and cardiovascular risk. The routine use of add-back hormone replacement has reduced these risks and increased patient compliance, making this group of drugs more useful as a medium-term treatment option. The estrogen threshold hypothesis highlights the concept of a ‘therapeutic window’ in which bone loss is minimal but the primary disease is not aggravated. It explains why add-back therapy is appropriate for such patients and helps to explain the basis behind new developments in the treatment of hormonally responsive gynaecological conditions such as gonadotrophin-releasing hormone antagonists and progesterone receptor modulators.
Case Rep Surg. 2015;
Endometriosis of the Vermiform Appendix within a Hernia Sac Infiltrating the Pubic Bone.
Purpose. Appendicular endometriosis mimicking appendicitis is a rare finding. Inguinal tumor in the course of appendicular endometriosis located within an inguinal hernia sac and infiltrating the periosteum of the pubic bone has not yet been described. Case Report. This paper describes a case of a rapidly enlarging, solid, unmovable, very painful upon palpation inguinal tumor, in a 36-year-old nulliparous woman. During surgery, a hard (approximately 4 cm in diameter) tumor infiltrating the periosteum of the right pubic bone and continuous with the inguinal hernia sac was dissected. The distal segment of the vermiform appendix was an element of the dissected tumor. Histological examination revealed endometriosis of the distal vermiform appendix. After 6 months of hormone treatment, she was referred for reoperation due to tumor recurrence. Once again histological examination of the resected tissue revealed endometriosis. There was no further recurrence of the disease with goserelin therapy. In addition to the case report, we present a review of the literature about endometriosisinvolving the vermiform appendix and the inguinal canal (Amyand’s hernia). Conclusion. This case expands the list of differential diagnoses of nodules found in the inguinal region of women.
Hum Mol Genet. 2015 Jul 1;24(13):3595-607
Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci.
Coetzee SG1, Shen HC2, Hazelett DJ3, Lawrenson K2, Kuchenbaecker K4, Tyrer J4, Rhie SK3, Levanon K5, Karst A6, Drapkin R7, Ramus SJ2; Ovarian Cancer Association Consortium, The Consortium of Investigators of Modifiers of BRCA1/2, Couch FJ7, Offit K8, Chenevix-Trench G9, Monteiro AN10, Antoniou A4, Freedman M11, Coetzee GA3, Pharoah PD4, Noushmehr H12, Gayther SA13; Ovarian Cancer Association Consortium The Consortium of Investigators of Modifiers of BRCA1/2.
Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer.
Ginekol Pol. 2015 Feb;86(2):94-9.
The role of chemokine and non-chemokine factors in pain-related complaints in patients with endometrial cysts.
Endometriosis is a chronic disease manifested as peritoneal endometrial implants and adhesions, as well as endometrial cysts, with pain as the dominant component.
The aim of the study was to evaluate the role of chemokine (MCP-1, MCP-2, MIP-1, MIP-1 and RANTES) and non-chemokine (urocortin, ghrelin, and leptin) factors in the intensity of pelvic pain in women with endometrial cysts.
MATERIAL AND METHODS:
A total of 86 women, aged 18-38, treated laparoscopically between September 2009 and November 2012, due to adnexal changes, i.e. endometrial cysts and mature teratomas, were recruited for the study. On a numeric rating scale, i.e. PSS (Pain Sensation Scale–according to Johnson), the patients rated pain intensity. The level of pain-related stress was investigated with the Pain Distress Scale (PDS, according to Johnson).
Medians for MCP-1, MCP-2, MIP-1, MIP-1 and RANTES concentrations were not statistically significantly different. The respondents rated pain intensity during menses as 6 and 3 points in the E and T groups, respectively (6 vs. 3 points; p=0.001). Statistically significant differences were also observed for pain intensity during work (apart from menses), (2 vs. 2 points, p=0,014) and during sexual intercourse (apart from menses) (3 vs. 1 points, p=0.006). Pain-related stress levels were higher in the T group as compared to the E group (3 vs. 5 points; p=0.007).
It seems safe to conclude that chemokines and leptin may play a significant role in the occurrence of pain complaints among women with endometrial cysts. Further research might result in implementation of new treatment methods for pain management, especially in terms of pharmacotherapy.
PLoS One. 2015 Mar 26;10(3
Compatibility of a novel thrombospondin-1 analog with fertility and pregnancy in a xenograft mouse model of endometriosis.
Endometriosis is a gynecological disease defined by the growth of endometrium outside of the uterus. Although endometriosis contributes to 50% of female infertility cases, medical treatments are incompatible with pregnancy. Angiogenesis, the growth of blood vessels from existing vasculature, plays a crucial role in endometriotic lesion growth and survival. Previously, we demonstrated the effectiveness of thrombospondin-1 analog, ABT-898 (Abbott Laboratories) to inhibit endometriotic lesion vascularization in mice. We have now evaluated the trans-generational implications of ABT-898 treatment before and during mouse pregnancy. We hypothesized that ABT-898 would target lesion vasculature without affecting pregnancy, offspring development, or ovarian and uterine vascularity in mice. Endometriosis was induced using human endometrium in β-estradiol-primed BALB/c-Rag-2-/-Il2rγ-/- mice receiving intraperitoneal injections of ABT-898 (25 mg/kg) or 5% dextrose control for 21 days. Ultrasound assessment of lesion vascularization revealed a reduction in blood flow supplying treated lesions. Excised ABT-898 treated lesions stained for CD31+ endothelial cells exhibited a decrease in microvessel density. Following confirmation of estrous cycling, mice were bred and treated with ABT-898 on gestation days 7, 9, 11, 13, 15, 17, and 19. ABT-898 did not affect estrous cycling or pregnancy parameters including litter size across generations and offspring weight gain. Quantification of angiogenic cytokine plasma levels revealed no significant differences between treatment groups. Vimentin staining of the uterus and ovary revealed no observable effects of ABT-898. Similarly, no obvious histological anomalies were observed in the kidney, liver, ovary, or uterus following ABT-898 treatment. These results suggest that ABT-898 effectively inhibit endometriotic lesion vascularization without affecting trans-generational pregnancy outcomes in mice.
Fertil Steril. 2015 Jun;103(6):1438-45.
Adverse pregnancy and birth outcomes associated with underlying diagnosis with and without assisted reproductive technology treatment.
To compare the risks for adverse pregnancy and birth outcomes by diagnoses with and without assisted reproductive technology (ART) treatment to non-ART pregnancies in fertile women.
Historical cohort of Massachusetts vital records linked to ART clinic data from Society for Assisted Reproductive Technology Clinic Outcome Reporting System.
Diagnoses included male factor (ART only), endometriosis, ovulation disorders, tubal (ART only), and reproductive inflammatory disorders (non-ART only). Pregnancies resulting in singleton and twin live births from 2004 to 2008 were linked to hospital discharges in women who had ART treatment (n = 3,689), women with no ART treatment in the current pregnancy (n = 4,098), and non-ART pregnancies in fertile women (n = 297,987).
MAIN OUTCOME MEASURE(S):
Risks of gestational diabetes, prenatal hospitalizations, prematurity, low birth weight, and small for gestational age were modeled using multivariate logistic regression with fertile deliveries as the reference group adjusted for maternal age, race/ethnicity, education, chronic hypertension, diabetes mellitus, and plurality (adjusted odds ratios [AORs] and 95% confidence intervals [CIs]).
Risk of prenatal hospital admissions was increased for endometriosis (ART: 1.97, 1.38-2.80; non-ART: 3.34, 2.59-4.31), ovulation disorders (ART: 2.31, 1.81-2.96; non-ART: 2.56, 2.05-3.21), tubal factor (ART: 1.51, 1.14-2.01), and reproductive inflammation (non-ART: 2.79, 2.47-3.15). Gestational diabetes was increased for women with ovulation disorders (ART: 2.17, 1.72-2.73; non-ART: 1.94, 1.52-2.48). Preterm delivery (AORs, 1.24-1.93) and low birth weight (AORs, 1.27-1.60) were increased in all groups except in endometriosis with ART.
The findings indicate substantial excess perinatal morbidities associated with underlying infertility-related diagnoses in both ART-treated and non-ART-treated women.
Gynecol Obstet Fertil. 2015 Apr;43(4):266-70.
Robotic assisted laparoscopy: comparison of segmentary colorectal resection and shaving for colorectal endometriosis.
To compare perioperative complications of two surgical methods for digestive endometriosismanagement: “shaving” and colorectal resection in robotic-assisted laparoscopy.
Twenty-eight women underwent robotic-assisted laparoscopy for digestive endometriosis, confirmed histologically. Six women had a digestive resection and twenty-one women had a shaving procedure. Short-term and long-term results and complications were compared between the two groups.
Operative time was significantly shorter (P=0.0002) and estimated blood loss was significantly lower (200 ml vs 560 ml, P=0.04) in the shaving procedure group in comparison with the resection group. We observed one conversion to laparotomy in the resection group and one case of bladder injury in the shaving group. Length of hospital stay was longer (P=0.0001) in the resection group than in the shaving group. At the two-month re-evaluation, there was no significant difference between the two groups for the number of women in full remission for pelvic pain, urinary or gastrointestinal symptoms or dyspareunia. Two women of the resection group reported functional gastrointestinal signs that persisted 24 months after the intervention.
Both immediate and delayed operative morbidity are more frequent in case of resection. Surgery for deep infiltrating endometriosis, even if operated with robotic assisted laparoscopy, is associated with significant morbidity.
J Assist Reprod Genet. 2015 May;32(5):699-704
Systemic oxidative stress could predict assisted reproductive technique outcome.
Previous studies have indicated that OxS (oxidative stress) may appear as a possible reason for poor ART outcome. Our aim was to study OxS levels in both partners of couples seeking Assisted reproduction Technology (ART).
Altogether 79 couples were recruited. Oxidative DNA damage (8-OHdG) and lipid peroxidation (8-EPI) were measured, and clinical background and ART outcomes were recorded.
Both OxS markers accurately reflected clinical conditions with prominent negative effects attributable to genital tract infections, endometriosis, uterine myoma and smoking. Furthermore, the level of OxS was also affected by partner’s state of health. The highest 8-EPI levels were detected in both partners when biochemically detectable pregnancies did not develop into clinically detectable pregnancies (in women, 97,8 ± 16,7 vs 72.9 ± 22,9, p = 0.007; in men, 89.6 ± 20,4 vs 72,1 ± 22,6, p = 0.049).
To conclude, high grade systemix OxS in both partners may negatively affect the maintenance and outcome of pregnancy. Applying the detection of OxS in ART patients may select patients with higher success rate and/or those who require antioxidant therapy. This would lead to improvement of ART outcome as well as natural fertility.
Evid Based Complement Alternat Med. 2015
The effects and possible mechanisms of puerarin to treat endometriosismodel rats.
Objective. To explore the effects of puerarin to treat endometriosis (EMT) model rats and the possible regulatory mechanisms. Methods. EMT model rats were surgically induced by autotransplantion of endometrial tissues. The appropriate dosage of puerarin to treat EMT model rats was determined by observing the pathologic morphology of ectopic endometrial tissues and by detecting the levels of estradiol (E2) and prostaglandin E2 (PGE2) of both serum and ectopic endometrial tissues. The related genes and proteins of ectopic endometrial tissues were analyzed by Real-time PCR and immunohistochemistry (IHC) to explore the possible mechanisms. Results. Puerarin could reduce the levels of E2 and PGE2 and prevent the growth of ectopic endometrium tissues by inhibiting the expression of aromatase cytochrome P450 (p450arom) and cyclooxygenase-2 (cox-2); puerarin could adjust the anabolism of E2 by upregulating the expression of 17β-hydroxysteroid-2 (17β-hsd-2) and downregulating the expression of 17β-hydroxysteroid-1 (17β-hsd-1) of the ectopic endometrium tissues; puerarin could increase the expression of ERβ and improve the inflammatory microenvironment of EMT model rats. Conclusions. Our data suggest that puerarin has a therapeutic effect on EMT model rats and could be a potential therapeutic agent for the treatment of EMT in clinic.
Am J Obstet Gynecol. 2015 Sep;213(3):262-7.
New insights in the pathophysiology of ovarian cancer and implications for screening and prevention.
Despite advances in medicine, ovarian cancer remains the deadliest of the gynecological malignancies. Herein we present the latest information on the pathophysiology of ovarian cancer and its significance for ovarian cancer screening and prevention. A new paradigm for ovarian cancer pathogenesis presupposes 2 distinct types of ovarian epithelial carcinoma with distinct molecular profiles: type I and type II carcinomas. Type I tumors include endometrioid, clear-cell carcinoma, and low-grade serous carcinoma and mostly arise via defined sequence either from endometriosis or from borderline serous tumors, mostly presenting in an early stage. More frequent type II carcinomas are usually high-grade serous tumors, and recent evidence suggests that the majority arise from the fimbriated end of the fallopian tube. Subsequently, high-grade serous carcinomas usually present at advanced stages, likely as a consequence of the rapid peritoneal seeding from the open ends of the fallopian tubes. On the other hand, careful clinical evaluation should be performed along with risk stratification and targeted treatment of women with premalignant conditions leading to type I cancers, most notably endometriosisand endometriomas. Although the chance of malignant transformation is low, an understanding of this link offers a possibility of prevention and early intervention. This new evidence explains difficulties in ovarian cancer screening and helps in forming new recommendations for ovarian cancer risk evaluation and prophylactic treatments.
Orv Hetil. 2015 Apr 5;156(14):552-7.
Reducing invasiveness of laparoscopic surgery using natural orifices and abdominal wall defects for extraction of the specimen.
Due to significant technical evolution complex surgeries can be performed laparoscopically nowadays. However, laparotomy is needed frequently for the extraction of the specimen, which decreases the advantages of laparoscopy.
The aim of the authors was to analyse and present their experience on the use of natural orifices and abdominal wall defects for extraction of the surgical specimen.
From 2009 the authors used natural orifices (stomach, vagina, rectum) when viscerotomy was an obligate part of laparoscopic surgery and, in a special gastrointestinal laparoscopic operation, the gate of the inguinal hernia for specimen extraction.
In 3 patients benign lesions of the stomach were extracted using gastroscope. In 6 patients with bowel endometriosis, in whom the wall of the vagina was completely infiltrated, the resected bowel was extracted transvaginally, and in 5 patients transrectal extraction of the specimen was performed. In 2 patients the inguinal hernia was used for the surgical specimen extraction after laparoscopic sigmoid resection, and in one patient a single-port was inserted into the gate of the hernia during laparoscopic cholecystectomy. Complications occurred only after transvaginal specimen extraction (rectovaginal fistula in 2 patients).
Use of natural orifices and abdominal wall defects for surgical specimen extraction further decreases the invasiveness of laparoscopic surgery, if indications made appropriately.
Eur J Obstet Gynecol Reprod Biol. 2015 Jun;189:1-7.
Meta-analysis of association between the TP53 Arg72Pro polymorphism and risk of endometriosis based on case-control studies.
In the light of the relationship between the TP53 Arg72Pro (rs1042522) polymorphism and the risk of endometriosis remains inclusive or controversial. For better understanding of the effect of TP53 Arg72Pro polymorphism on endometriosis risk, we performed a meta-analysis.
The relevant studies were identified through a search of PubMed, Web of Science, EMBASE, Ovid, Springer, China National Knowledge Infrastructure (CNKI), cqvip, Wanfang database, and Chinese Biomedical Literature (CBM) databases up to December, 2014. The association between the TP53 Arg72Pro polymorphism and endometriosis risk was pooled by conducted by odds ratios and 95% confidence intervals.
A total of fifteen case-control studies with 2683 cases and 3335 controls were eventually identified. There was significant association between Arg72Pro polymorphism and endometriosis risk in all of the five models in overall populations (C vs. G: OR=1.32, 95%CI=1.14-1.53, p=0.00; CC vs. GG: OR=1.80, 95%CI=1.28-2.53, p=0.001; GC vs. GG: OR=1.52, 95%CI=1.22-1.88, p=0.00; CC vs.
OR=1.32, 95%CI=1.05-1.66, p=0.016; CC/GC vs. GG: OR=1.59, 95%CI=1.26-2.00, p=0.00). In the sub-group analysis according to ethnicity, the results suggested that TP53 Arg72Pro polymorphism was not associated with endometriosis risk in Caucasians. However, the significant association was found in Asians and Mixed race (MIX) under the five models.
The results of this meta-analysis suggest that the TP53 Arg72Pro polymorphism can increase the risk of endometriosis, especially among Asians and MIX populations. Considering the limited sample size and ethnicities included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results.
Vet J. 2015 May;204(2):150-6.
The association of subclinical hypocalcemia, negative energy balance and disease with bodyweight change during the first 30 days post-partum in dairy cows milked with automatic milking systems.
In a prospective cohort study, the daily bodyweight (BW) and milk production of 92 cows were recorded using automatic milking systems. The objectives were to characterize calcium serum concentration variability on days 1-3 post-partum and to evaluate the association between subclinical hypocalcemia (SHPC) and change in BW over the first 30 days in milk (DIM) in Holstein dairy cows, while controlling for concurrent disease and negative energy balance (NEB). SHPC was defined as total serum calcium concentration between 6 and 8 mg/dL, NEB was defined as non-esterified fatty acids (NEFA) > 0.7 mEq/L or β-hydroxybutyrate (BHB) ≥ 1.2 mmol/L. The peak incidence of SHPC was at 1 DIM for all groups (11%, 42% and 60% for parities 1, 2, and ≥3, respectively). All parity groups lost weight (21, 33, and 34 kg) during the first 30 DIM. Parity 1 animals with disease compared with those without disease lost the most weight (2.6 kg/day BW loss vs. <1.9 kg/day, respectively). Normocalcemic parity 2 animals with either NEB or disease lost the most weight (>5 kg/day) compared with those in the SHPC group (≤4.5 kg/day). In parity ≥ 3 animals, SHPC was an important factor for BW loss; SHPC animals lost the most weight (>3.7 kg/day) vs. normocalcemic cows (≤3.3 kg/day) regardless of NEB or disease status. Even though all animals lost weight during early lactation the effect of disease, NEB, and SHPC on BW loss was different in each parity group.
Med Sci Monit. 2015 Mar 28;21:915-20.
MiR-191 modulates malignant transformation of endometriosis through regulating TIMP3.
Although aberrant expression of several miRNAs was found during the pathological development of endometriosis to endometriosis-associated ovarian cancer (EAOC), their roles are not fully understood. miR-191 is a miRNA significantly upregulated in endometriosis and EAOC patients. However, its downstream network is still not clear. This study explored its role in malignant transformation of endometriosis to EAOC.
MATERIAL AND METHODS:
Tissues from 12 healthy controls, 12 patients with endometriomas, and 12 patients with EAOC were used to verify miR-191 expression by using qRT-PCR. Endometriosis cell line CRL-7566 and ovarian endometrioid carcinoma cell line CRL-11731 were used to explore the downstream regulative function of miR-191.
By using tissue and serum samples from healthy, endometriosis, and EAOC participants, we confirmed that miR-191 expression was significantly higher in endometriosis and EAOC participants. Interestingly, we also observed that TIMP3 expression was negatively correlated with miR-191 expression. Overexpressing miR-191 in CRL-7566 significantly increased cell proliferation and invasion, while miR-191 knockdown in CRL-11731 cells significantly decreased cell proliferation and invasion. These modulating effects of miR-191 are achieved through its regulation of TIMP3.
miR-191 can directly regulate TIMP3 expression, thereby affecting cell proliferation rate and invasion ability. The miR-191-TIMP3 axis might be critical in the malignant transformation of endometriosis to EAOC.
J Minim Invasive Gynecol. 2015 Jul-Aug;22(5):813-9.
Laparoendoscopic Single-site Compared With Conventional Laparoscopic Ovarian Cystectomy for Ovarian Endometrioma.
To estimate the efficacy of laparoendoscopic single-site (LESS) ovarian cystectomy in ovarian endometrioma.
Retrospective study. Canadian Task Force Classification II-2.
Three hundred forty-three premenopausal women with previously untreated ovarian endometrioma.
The surgical and follow-up outcomes were compared between LESS (n = 154) and conventional laparoscopic ovarian cystectomy (n = 189).
MEASUREMENTS AND MAIN RESULTS:
Four patients (2.6%) in the LESS group but no patients in conventional group required additional ports (p = .040). No patient in either group required conversion to laparotomy. Operating times, estimated blood loss, perioperative hemoglobin level changes, and transfusions did not differ between groups. However, the length of postoperative hospital stay was significantly shorter in the LESS group (2 ± .4 days vs 2.3 ± .8 days, p = .001) and significantly more patients in this group were discharged within 2 days of surgery (93.5% vs 79.4%, p < .001). Perioperative complications occurred in 1 patient (0.6%) in the LESS group and in 2 patients (1.1%) in the conventional group (p > .999). The LESS group showed significantly lower pain scores at 16 (3.2 vs 3.6, p < .001), 24 (2.8 vs 3, p = .004), and 30 hours (2.7 vs 3, p = .040) after surgery. The requirement for additional analgesics was significantly lower in the LESS group (27.9% vs 45%, p = .001). After a median follow-up time of 48 months, 11 patients (7.1%) in the LESS group and 21 patients (11.1%) in the conventional group showed recurrent endometrioma (p = .209).
LESS ovarian cystectomy has similar feasibility and efficacy with conventional laparoscopic surgery in the management of endometrioma. However, LESS is associated with less postoperative pain, lower analgesic requirement, and earlier discharge.
Reprod Sci. 2015 Sep;22(9):1134-42.
H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis.
Epigenetic mechanisms may play an important role in the etiology of endometriosis. The modification of histones by methylation of lysine residues has been shown to regulate gene expression by changing chromatin structure. We have previously shown that endometriotic lesions had aberrant levels of histone acetylation (lower) and methylation (higher) than control tissues. We aimed to determine the levels of trimethylated histone 3 at lysine residue 27 (H3K27me3), a well-known repressive mark, by immunoassay of fresh tissues and immunohistochemistry (IHC) of an endometriosis-focused tissue microarray. Also, we aimed to determine levels of expression of enhancer of zeste homolog 2 (EZH2), the enzyme responsible for trimethylation of H3K27me3, in cell lines. Average levels of H3K27me3 measured by immunoassay were not significantly different in lesions compared to endometrium from patients and controls. However, there was a trend of higher levels of H3K27me3 in secretory versus proliferative endometrium. The results of IHC showed that lesions (ovarian, fallopian, and peritoneal) and secretory endometrium from controls have higher percentage of H3K27me3-positive nuclei than eutopic endometrium from patients. Endometriotic epithelial cells express high levels of EZH2, which is upregulated by progesterone. This study provides evidence in support of a role of H3K27me3 in the pathogenesis of endometriosis and for EZH2 as a potential therapeutic target for this disease, but more studies are necessary to understand the molecular mechanisms at play.
Am Fam Physician. 2015 Mar 1;91(5):308-14.
Evaluation and treatment of infertility.
Infertility is defined as the inability to achieve pregnancy after one year of regular, unprotected intercourse. Evaluation may be initiated sooner in patients who have risk factors for infertility or if the female partner is older than 35 years. Causes of infertility include male factors, ovulatory dysfunction, uterine abnormalities, tubal obstruction, peritoneal factors, or cervical factors. A history and physical examination can help direct the evaluation. Men should undergo evaluation with a semen analysis. Abnormalities of sperm may be treated with gonadotropin therapy, intrauterine insemination, or in vitro fertilization. Ovulation should be documented by serum progesterone level measurement at cycle day 21. Evaluation of the uterus and fallopian tubes can be performed by hysterosalpingography in women with no risk of obstruction. For patients with a history of endometriosis, pelvic infections, or ectopic pregnancy, evaluation with hysteroscopy or laparoscopy is recommended. Women with anovulation may be treated in the primary care setting with clomiphene to induce ovulation. Treatment of tubal obstruction generally requires referral for subspecialty care. Unexplained infertility in women or men may be managed with another year of unprotected intercourse, or may proceed to assisted reproductive technologies, such as intrauterine insemination or in vitro fertilization.
Reprod Sci. 2015 Sep;22(9):1129-33.
Anti-Müllerian Hormone in Peritoneal Fluid and Plasma From Women With and Without Endometriosis.
Anti-Müllerian hormone (AMH) has potential local effects on ovarian function and endometrial tissue, including endometriosis, but its presence in peritoneal fluid is not fully understood. This is a cross-sectional study evaluating AMH in peritoneal fluid and plasma from women with endometriosis (N = 61) and from control women without endometriosis (N = 36). There was a significant correlation between AMH in plasma and peritoneal fluid from both patients with endometriosis (r(2) = .767 [P < .001]) and control participants (r(2) = .647 [P < .001]) less than 45 years of age. Anti-Müllerian hormone declined with women’s increasing age in both plasma and peritoneal fluid in women with and without endometriosis. There were no differences in the plasma or peritoneal fluid AMH in women with endometriosis versus control women. The strong relationship between plasma and peritoneal fluid may allow plasma AMH to be a marker for peritoneal AMH in studies evaluating the local effects of AMH.
J Ovarian Res. 2015 Feb 25;8:4.
Use of aromatase inhibitors in practice of gynecology.
The conversion of androgens into estrogens by aromatase is called aromatization and is inhibited by aromatase inhibitors (AIs). The aim of this article is to evaluate the use of aromatase inhibitors in gynecological diseases such as endometriosis, leiomyoma, estrogen- dependent gynecologic neoplasia and infertility.
This is a review of literature combined with experience and use of aromatase inhibitors ın practıce of gynecology.
AIs are promising agents in treatment of estrogen dependent disease. However lack of experience, side effects and cost are limiting factors for using these agents in infertility treatment. However there is need for larger, well designed randomized trials to generate robust data in order to establish the true potential of aromatase inhibitors
Rom J Morphol Embryol. 2015;56(1):133-8.
The immunoprofile of interstitial Cajal cells within adenomyosis/endometriosis lesions.
Adenomyosis and endometriosis are lesions which have aroused the interest for the investigation of antibodies specific to the structures from the composition, but also for the cause behind the appearance of these lesions in completely different structures. The impact they have on fertility is not known entirely, for they are difficult to diagnose. Endometriosis causes infertility and it is a hard to treat lesion. The research performed in the last years has been focused on the so-called linkage analysis, or reverse genetics. It refers to identifying the genes which are prone to developing this affection. We investigated clinically 40 female inpatients (n=40) who had underwent genital surgery and received a variegate diagnosis in the “Sf. Ioan” Emergency Hospital, Bucharest, Romania, between January-September 2014 and also their histopathology and immunohistochemistry. We proceeded with the histopathology examination in order to establish a diagnosis in respect to the admission diagnosis and then, using the ABC (Avidin-Biotin complex) method, we analyzed the immunohistochemistry of the following markers: S100 protein (for detection of ganglia and nerve cells), CD117÷c-kit (selective detection of interstitial Cajal cells – ICC), desmin and vimentin (intermediary filaments for detecting ICC-like cells, which cohabit with uterine myocytes and are not contractile cells) and CD10 (a sensitive and useful immunomarker in the diagnosis of endometrial stroma and, in some cases, of neoplasia). Our study, regarding the immunoprofile of some markers of adenomyosis÷endometriosis lesions, supports the hypothesis that the interstitial Cajal cells are non-reactive, they are not in relationship with investigated lesions, but CD10 is a very useful marker to highlight the endometrial stroma in query cases.
Rom J Morphol Embryol. 2015;56(1):295-300.
Thoracic endometriosis with a long delay in diagnosis.
This paper describes a case of thoracic endometriosis in 36-year-old woman with a long delay in diagnosis. At the admission in the hospital, the patient had a medical history of persistent dysmenorrhea since the age of 13, infertility and an episode of total right pneumothorax two months ago successfully resolved by minimum pleurotomy of the right hemitorax. She came with moderate pain on right hemithorax and dyspnea, which occurred on the first day of menstruation but she did not have any other respiratory symptoms such as hemoptysis, cough. Radiological imaging (chest radiography and computer tomography) at the time of admission confirmed recurrence of the right pneumothorax. She underwent surgical treatment of the right pneumothorax using a single-port video-assisted approach. Intraoperative macroscopic lesions were found catamenial pneumothorax characteristic diagnosis and biopsy material taken (parietal pleura) for histopathology. Immuno-histochemical tests confirmed the diagnosis of thoracic endometriosis. The gonadotropin-releasing hormone analogue was received by the patient early after surgery and there was no clinical or radiological recurrence at a four months follow-up.
Ginecol Obstet Mex. 2014 Nov;82(11):755-63.
Endometriosis. Why is not removed by the immune system?.
Endometriosis is a gynecological inflammatory and estrogen dependent pathology, defined as the presence of endometrial tissue outside the uterine cavity. The two most common symptoms of endometriosis are pelvic pain and infertility. This pain can be so intense that it affects the quality of life of women, from their relationships to their daily activities. Approximately 10% of women of reproductive age suffer from this disease. The main objective of this work was to investigate which immune system abnormalities present in patients with endometriosis that prevents ectopic endometrial tissue removal. Here we describe a series of changes in the different types of leukocytes, cytokines and factors that regulate the immune response seen in patients with endometriosis and the mechanisms by which these changes, not only favor “immunological tolerance” to the endometrial implants but at the same time stimulate the development of the disease by increasing cell proliferation and angiogenesis and inhibition of apoptosis ectopic endometrial tissue.
BMJ Case Rep. 2015 Mar 31;2015.
Jack in the box: inguinal endometriosis.
A 39-year-old woman with a left-sided inguinal swelling was referred to us with a diagnosis of inguinal hernia. On asking leading questions, the patient gave a typical history of cyclical pain and increased swelling during menstruation. Fine-needle aspiration biopsy revealed endometrial glands. Preoperatively, the extent of the endometriotic lesion was delineated using MRI. The lesion was approached through the patient’s caesarean scar for cosmetic reasons and excised in toto. Final diagnosis was round ligament endometriosis. The patient was asymptomatic at 3, 6 and 12 months’ follow-up. This case re-emphasises the fact that endometriosis is an enigmatic disease and can be found anywhere in the body. Thus, a woman of reproductive age presenting with any cyclical symptom should be asked about its relation to her menstrual cycle.
J Obstet Gynaecol Res. 2015 Aug;41(8):1300-4.
Rare case of giant cystic adenomyoma mimicking a uterine malformation, diagnosed and treated by hysteroscopy.
We describe a case of giant cystic uterine adenomyoma that was diagnosed and treated by hysteroscopy. In a 27-year-old woman with menometrorrhagia, severe dysmenorrhea, and chronic pelvic pain, pelvic ultrasonography revealed an enlarged uterine cavity filled with homogeneous low echogenic fluid content. A large cornual hematometra of 8.0 cm in diameter in a bicornuate uterus was suspected, and this hypothesis was also supported by magnetic resonance imaging findings. On the contrary, hysteroscopy revealed a bilocular huge cystic lesion of the posterior uterine wall that was removed by means of monopolar loop resection. The operative finding and the histopathologic examination confirmed the diagnosis of cystic adenomyoma of the uterus. Hysteroscopy may represent a valid tool for diagnosis and minimally invasive treatment of cystic adenomyoma, including those of large volume. Its use is helpful in differential diagnosis between cystic adenomyoma and uterine malformations as a possible cause of pelvic pain.
J Obstet Gynaecol Res. 2015 Aug;41(8):1234-9.
Exploratory study of pre-surgical medications with dienogest or leuprorelin in laparoscopic cystectomy of endometrial cysts.
The aim of this study was to compare the effects of pre-surgical medication with dienogest or leuprorelin on post-surgical ovarian function.
MATERIAL AND METHODS:
We conducted an exploratory study in two centers in Japan that comprised 30 patients with ovarian endometrial cysts for whom surgical excision was planned. Patients were enrolled and divided into pre-surgical medication groups with dienogest or leuprorelin for 12 weeks. Thereafter, patients were treated by laparoscopic cystectomy. The primary outcome was ovarian function post-surgery, as assessed by serum anti-Müllerian hormone (AMH) level, antral follicle count (AFC) and resumption of menses. Secondary outcome was the effect of pre-surgical medication, as assessed by the size of endometrial cysts and visual analog scale (VAS) score. Serum AMH, AFC, size of endometrial cysts, and VAS scores were measured at baseline (before medication), after medication (1 day before surgery), and at 4 and 12 weeks post-surgery.
Serum AMH levels did not change after pre-surgical medication with either dienogest or leuprorelin. Although AMH decreased after surgery, it recovered by 12 weeks post-surgery in both groups with no statistically significant difference. Mean AFC did not change after surgery in either group. Menses returned by 12 weeks post-surgery in all patients except for those who were pregnant. The rate of reduction of endometrial cyst volume did not differ between the groups. Both dienogest and leuprorelin were associated with substantial reductions in VAS scores.
There were no statistically significant differences between pre-surgical medication with dienogest and leuprorelin in post-surgical ovarian function. Both medications were effective in reducing endometrial cyst volume and VAS score.
Afr Health Sci. 2014 Dec;14(4):913-8.
Serum HE4 is more suitable as a biomarker than CA125 in Chinese women with benign gynecologic disorders.
This study measured the human epididymis protein 4 (HE4) and CA125 levels in Chinese women with benign gynecological disorders.
MATERIAL AND METHODS:
Sera were obtained from Chinese women prior to surgery for a pelvic mass and HE4 and CA125 levels were determined. The proportions of patients with HE4 and CA125 levels were compared.
There were 68 Chinese women with benign diseases. HE4 levels were less elevated than CA125 (1% V.S. 29%, P<0.001). The significant difference was observed in patients with endometriosis/endometriomas in which HE4 was not elevated patients and CA125 was elevated in 53% (P<0.001). Serum HE4 level was not elevated in patients with cystadenoma (0% V.S. 23%, P<0.001) and in patients with germ cell tumors (0% V.S. 5%, P<0.001).
HE4 was less elevated and more suitable as a biomarker than CA125 in chinese women with benign disease.
Cancer Biomark. 2015;15(4):493-9.
Cyst fluid iron-related compounds as useful markers to distinguish malignant transformation from benign endometriotic cysts.
The purpose of this study was to investigate cyst fluid levels of total iron, heme iron and free iron in benign endometriotic cysts and endometriosis-associated ovarian cancer (EAOC) and to demonstrate the significance of these biomarkers in differential diagnosis between EAOC and endometriotic cysts.
Cyst fluid samples were obtained from eleven patients with EAOC and thirty-six women with benign endometriotic cysts at the time of surgery.
The median (± SD) total iron levels for endometriotic cysts and EAOC cysts were 244.4 ± 204.9 mg/L and 14.2 ± 36.6 mg/L, respectively. EAOC patients had much lower levels of iron-related compounds compared with endometriotic cyst samples (p< 0.001). When the total iron results were analyzed using the receiver operating characteristics (ROC) curve method, the optimum diagnostic cut-off point was 64.8 mg/L, sensitivity was 90.9%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 97.3%. Patient demographic characteristics such as tumor size, age at operation, parity and menopause were not correlated with cyst fluid iron levels.
We conclude for the first time that iron-related compounds are important biomarkers that can predict malignant transformation with high sensitivity and specificity for women with endometriosis.
Eur J Obstet Gynecol Reprod Biol. 2015 May;188:45-50.
Aromatase inhibitor (anastrozole) affects growth of endometrioma cells in culture.
To study the effects of aromatase inhibitor (anastrozole) on the growth and estradiol secretion of endometrioma cells in culture.
Endometrioma cells are grown in vitro until maximum growth before used in this study. This was done in the research laboratory for tissue culture, in an academic hospital.
Testosterone at a concentration of 10 μg/mL was added as a substrate for the intracellular aromatase. In addition, aromatase inhibitor was added at a concentration of 200 and 300 μg/mL. The effect on cell growth and estradiol secretion is evaluated using Student’s t-test.
The use of testosterone increased estradiol secretion by endometrioma cells in culture. The use of aromatase inhibitor significantly inhibited the growth of endometrioma cells, and estradiol secretion.
Aromatase inhibitor (anastrozole) may be an effective treatment for endometriosis due to inhibition of cellular aromatase.