Environ Toxicol Pharmacol. 2017 Apr;51:56-70.
Human exposure to endocrine disrupting chemicals: effects on the male and female reproductive systems.
Endocrine disrupting chemicals (EDCs) comprise a group of chemical compounds that have been examined extensively due to the potential harmful effects in the health of human populations. During the past decades, particular focus has been given to the harmful effects of EDCs to the reproductive system. The estimation of human exposure to EDCs can be broadly categorized into occupational and environmental exposure, and has been a major challenge due to the structural diversity of the chemicals that are derived by many different sources at doses below the limit of detection used by conventional methodologies. Animal and in vitro studies have supported the conclusion that endocrine disrupting chemicals affect the hormone dependent pathways responsible for male and female gonadal development, either through direct interaction with hormone receptors or via epigenetic and cell-cycle regulatory modes of action. In human populations, the majority of the studies point towards an association between exposure to EDCs and male and/or female reproduction system disorders, such as infertility, endometriosis, breast cancer, testicular cancer, poor sperm quality and/or function. Despite promising discoveries, a causal relationship between the reproductive disorders and exposure to specific toxicants is yet to be established, due to the complexity of the clinical protocols used, the degree of occupational or environmental exposure, the determination of the variables measured and the sample size of the subjects examined. Future studies should focus on a uniform system of examining human populations with regard to the exposure to specific EDCs and the direct effect on the reproductive system.
Iran J Med Sci. 2017 Jan;42(1):98-101.
Ruptured Hemorrhagic Cyst of Undescended Ovary Mimicking Mucocele: A Rare Pediatric Case.
Undescended ovary is a rare entity and usually presentedas a case report. It is associated with urinary and uterine anomalies. Symptomatic patients are diagnosed during surgery. Most of the patients are asymptomatic and treatment is unnecessary. They are incidentally diagnosed during infertility evaluation and treatment such as ovarian hyperstimulation studies. A 15-year-old female patient presented with the diagnosis of renal cystic massas identifiedduring ultrasonography in another hospital. Abdominal computedtomography image was requested. A cystic lesion of about 48×34 mm with well-defined borders associated with the appendix and probably with mucocele of the appendix was reported in the lower right abdominal quadrant close to the cecum. During exploration, the right ovary was seen to be attached to the cecum and was higher in position as well as a right ovary originated cystic structure of 5×5 cm. Using needle aspiration, intraovarian hemorrhage was confirmed and partial cystectomy was performed. The present study reports on an undescended ovary that hadacute abdomen symptoms imitating mucocele. In girls referring to the hospital with abdominal pain, although quite rare, undescended ovaries are to be also considered. As the incidence of renal and uterine anomalies is higher in suchpatients, in symptomatic cases relevant organs are to be investigated carefully during surgical intervention.
Cancer Causes Control. 2017 May;28(5):437-445.
Endometriosis and risk of ovarian and endometrial cancers in a large prospective cohort of U.S. nurses.
Endometriosis is associated with ovarian cancer, but the relation with endometrial cancer is unclear. Prior studies generally were retrospective and had potential limitations, including use of self-reported endometriosis, failure to account for delays between symptom onset and endometriosis diagnosis, and changes in risk factors post-endometriosis diagnosis. We evaluated whether these limitations obscured a weak association with endometrial cancer and the extent to which these limitations impacted associations with ovarian cancer.
Cox proportional hazards regression models were used to assess associations between endometriosis and cancer risk, evaluating the impacts of self-reported vs. laparoscopically confirmed endometriosis, delayed diagnosis, and post-endometriosis diagnosis changes in risk factor exposures on relative risk estimates.
Over 18 years of follow-up, we identified 228 ovarian and 166 endometrial cancers among 102,025 and 97,109 eligible women, respectively. Self-reported endometriosis was associated with ovarian cancer [relative risk (RR): 1.81; 95% confidence interval (CI): 1.26-2.58]; this association was stronger for laparoscopically confirmed endometriosis (HR: 2.14; 95% CI 1.45-3.15). No association was observed with endometrial cancer (self-report RR: 0.78; 95% CI 0.42-1.44; laparoscopic-confirmation RR: 0.76; 95% CI 0.35-1.64). Accounting for diagnosis delays or post-endometriosis diagnosis changes in risk factors had a little impact.
This study adds to the evidence that endometriosis is not strongly linked to endometrial cancer risk and that the association with ovarian cancer is robust to misclassification, diagnostic delay, and changes in exposures post-endometriosis diagnosis. Our analysis suggests that confounding and misclassification do not obscure a weak association for endometrial cancer risk, although our results should be replicated.
Cell Death Dis. 2017 Mar 16;8(3):e2666.
IL-27 triggers IL-10 production in Th17 cells via a c-Maf/RORγt/Blimp-1 signal to promote the progression of endometriosis.
Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10+Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-β. Compared with peripheral CD4+ T cells, endometrial CD4+ T cells highly expressed IL-27 receptors, especially the ectopic endometrium. Under external (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and local (estrogen, IL-6 and TGF-β) environmental regulation, IL-27 from macrophages and endometrial stromal cells (ESCs) induces IL-10 production in Th17 cells in vitro and in vivo. This process may be mediated through the interaction between c-musculoaponeurotic fibrosarconna (c-Maf) and retinoic acid-related orphan receptor gamma t (RORγt), and associated with the upregulation of downstream B lymphocyte-induced maturation protein-1 (Blimp-1). IL-10+Th17 cells, in turn, stimulate the proliferation and implantation of ectopic lesions and accelerate the progression of endometriosis. These results suggest that IL-27 is a pivotal regulator in endometriotic immune tolerance by triggering Th17 cells to produce IL-10 and promoting the rapid growth and implantation of ectopic lesions. This finding provides a scientific basis for potential therapeutic strategies aimed at preventing the development of endometriosis, especially for patients with high levels of IL-10+Th17 cells.
J Pediatr Surg. 2017 Aug;52(8):1269-1272.
Unexpected findings after surgery for suspected appendicitis rarely change treatment in pediatric patients; Results from a cohort study.
To determine if non-operative treatment is safe in children with acute appendicitis, we evaluated the incidence of unexpected findings after an appendectomy in children, and the influence they have on subsequent treatment.
A historical cohort study (January 2004-December 2014) was performed including children, aged 0-17 years, who underwent an appendectomy for the suspicion of acute appendicitis. Patients were divided based upon histopathological examination. Unexpected findings were reviewed, as well as the subsequent treatment plan.
In total 484 patients were included in this study. In the overall group, unexpected findings were noted in 10 (2.1%) patients of which two patients intra-operatively with a non-inflamed appendix (Ileitis terminalis N=1 and ovarian torsion N=1) and in 8 patients on histopathological examination. The latter group consisted of 4 patients with concomitant simple appendicitis (parasitic infection N=3 and Walthard cell rest N=1), two with concomitant complex appendicitis (carcinoid N=1 and parasitic infection N=1) and two patients with a non-inflamed appendix (endometriosis N=1 and parasitic infection N=1). Treatment was changed in 4 patients (<1%).
Results from this study corroborate the safety of non-operative strategy for acute simple appendicitis, as the occurrence of unexpected findings was low, with extremely few necessary changes of the treatment plan because of serious findings.
Aust N Z J Obstet Gynaecol. 2017 Apr;57(2):201-205.
Endometriosis in patients with irritable bowel syndrome: Specific symptomatic and demographic profile, and response to the low FODMAP diet.
Women with endometriosis are frequently misdiagnosed with irritable bowel syndrome (IBS) for some time before a correct diagnosis is made. Visceral hypersensitivity is a key feature in both conditions.
To determine if there are distinct symptom patterns in women with IBS and endometriosis, and to determine the response of these women to a low FODMAP diet in comparison to those with IBS alone.
MATERIALS AND METHODS:
A retrospective analysis of prospectively collected data from women attending a specialist IBS service in Christchurch New Zealand. Data from those who met Rome III criteria for IBS were sorted into two groups: concurrent endometriosis and those with IBS alone. Demographics and symptom patterns were identified from a prospective questionnaire. A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet was taught to all women as the primary therapeutic intervention. Responses to the diet were noted against their ultimate disposition.
Of the 160 women who met Rome III criteria for IBS, 36% had concurrent endometriosis. The presence of dyspareunia (P > 0.0001), referred pain (P = 0.005), bowel symptoms exacerbated by menstruation (P = 0.0004) and a family history of endometriosis (P = 0.0003) were associated with concurrent endometriosis. Seventy two percent of these women reported a >50% improvement in bowel symptoms after four weeks of a low FODMAP diet compared with 49% in those with no known endometriosis (P = 0.001, odds ratio 3.11, 95% CI, 1.5-6.2).
Women with concurrent endometriosis and IBS report a unique symptom phenotype. The low FODMAP diet appears effective in women with gut symptoms and endometriosis.
Sci Rep. 2017 Mar 17;7:44616.
Effects of matrix stiffness on epithelial to mesenchymal transition-like processes of endometrial epithelial cells: Implications for the pathogenesis of endometriosis.
Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites. Our previous study revealed an epithelial to mesenchymal transition (EMT)-like process in red peritoneal endometriosis, whereas membrane localization of E-cadherin was well maintained in epithelial cells of deep infiltrating endometriosis (DIE). Here we show that endometrial epithelial cells (EEE) grown on polyacrylamide gel substrates (PGS) of 2 kilopascal (kPa), a soft matrix, initiate a partial EMT-like process with transforming growth factor-β1 (TGF-β1) stimulation. Increasing matrix stiffness with TGF-β1 stimulation reduced the number of cell-cell contacts. Cells that retained cell-cell contacts showed decreased expression of E-cadherin and zonula occludens 1 (ZO-1) to cell-cell junctions. Few deep endometriotic epithelial cells (DEE) grown on 30-kPa PGS, which may mimic in vivo tissue compliance of DIE, retained localization of E-cadherin to cell-cell junctions with TGF-β1 treatment. Immunohistochemical analysis showed no phosphorylated Smad 2/3 nuclear localization in E-cadherin+ epithelial cells of DIE. We hypothesize that EEE may undergo an EMT-like process after attachment of endometrium to peritoneum in a TGF-β1-rich microenvironment. However, TGF-β1 signaling may be absent in DIE, resulting in a more epithelial cell-like phenotype in a rigid microenvironment.
Eur J Obstet Gynecol Reprod Biol. 2017 May;212:9-12.
Effects of long-term postoperative dienogest use for treatment of endometriosis on bone mineral density.
This study was conducted to evaluate the effects of long-term postoperative dienogest (DNG) use for the treatment of endometriosis on bone mineral density (BMD).
Sixty reproductive-aged women who underwent conservative surgery for endometriomas and received postoperative DNG (2mg/day) for at least 12 months to prevent recurrence were analyzed. BMD was measured before and after DNG treatment by using dual energy X-ray absorptiometry, and changes in BMD were evaluated.
Mean patient age was 30.5 years, and mean duration of DNG treatment was 18.6 months. BMD at the lumbar spine significantly decreased after the first 6 months (-2.2%), and 1year (-2.7%) of DNG treatment, compared to baseline. The proportion of women who had significantly decreased BMD at the lumbar spine after 1year was 75% (45/60). In addition, BMD at the femur neck also decreased significantly after 1year (-2.8%). BMDs after 2 years were not different from those after 1year at both sites in 24 women who received DNG for ≥2years. In addition, there were no differences in baseline characteristics between women who had significantly reduced BMD at the lumbar spine after 1year (N=45) and women who did not (N=15).
This study suggests that long-term postoperative DNG treatment might have an adverse effect on BMD in reproductive-aged women. Bone loss mostly occurs during the first 6 months of treatment with DNG. A clinical trial is warranted to establish the effects of long-term DNG treatment on bone mass.
Int J Surg Case Rep. 2017;33:139-142
A case report of thoracic endometriosis – A rare cause of haemothorax.
The presence of endometrial tissue in airways, pleura and lung parenchyma is called thoracic endometriosis syndrome (TES). It is a rare pathology, and typically consists of catamenial pneumothorax, haemothorax, haemoptysis, and pulmonary nodules. We report a case of a 36-year-old woman with thoracic endometriosis causing catamenial haemothorax.
The diagnosis of thoracic endometriosis is complicated and often delayed. TES should be suspected in a reproductive age woman with exacerbating symptoms during the menstruation. Treatment may be medical and surgical.
Abdom Radiol (NY). 2017 Jul;42(7):1975-1992.
Adnexal masses associated with peritoneal involvement: diagnosis with CT and MRI.
Given the unique intra-peritoneal anatomic location of the adnexa, tubo-ovarian diseases can commonly spread into the peritoneal cavity. Peritoneal seeding may occur in a spectrum of adnexal conditions including infectious diseases, endometriosis, and benign or malignant primary or secondary ovarian tumors. CT is usually the imaging modality on which the concomitant involvement of the peritoneum and the ovary is depicted. The first diagnosis to be considered by the radiologist is generally peritoneal carcinomatosis from ovarian cancer but other conditions cited above have also to be borne in mind and may be suggested on the basis of careful assessment of CT findings or on further MR findings. MRI may indeed help characterize the lesions in some cases. The purpose of this review is to describe the clinical and imaging patterns of peritoneal involvement that may be found in association with different ovarian lesions. Familiarity with these patterns and diagnoses will help the radiologist narrow the differential diagnosis and make an accurate diagnosis, thus facilitating patient management and avoiding unnecessary invasive treatment.
Int J Gynecol Pathol. 2018 Jan;37(1):44-51.
Microcystic, Elongated, and Fragmented Pattern Invasion in Ovarian Endometrioid Carcinoma: Immunohistochemical Profile and Prognostic Implications.
Microcystic, elongated, and fragmented (MELF) pattern invasion is a poor prognostic indicator in uterine endometrioid carcinoma, but its existence, biology, and prognostic value have not been described in ovarian endometrioid carcinoma. We evaluated cases of ovarian endometrioid carcinoma without synchronous uterine endometrioid carcinoma for MELF and other histologic features. To evaluate tumor biology, we assessed an immunohistochemical profile, including MLH1, PMS2, MSH2, MSH6, β-catenin, e-cadherin, CK19, and cyclin D1. A retrospective chart review evaluated clinical and demographic features and survival. The Fisher exact test analyzed data. The Kaplan-Meier method assessed overall survival. Forty-two patients met inclusion criteria. MELF was found in 45%. Two MELF cases showed MSH2/MSH6 deficiency and 2 conventional cases showed PMS2 deficiency. Clear cell features were seen exclusively in MELF cases (P-value=0.044). No difference was identified in overall survival, cancer recurrence, serous features, concurrent endometriosis, lymphovascular space invasion, lymph node metastasis, bilaterality of disease, extranodal metastasis, or remainder of immunohistochemical profile. MELF occurs at similar rates in ovarian endometrioid carcinoma and uterine endometrioid carcinoma and can be helpful in defining ovarian endometrioid carcinoma as it proves definitive invasion. Recurrence and overall survival in ovarian endometrioid carcinoma are not affected by MELF. Clear cell features are identified exclusively in MELF cases. Different mismatch repair proteins are lost in MELF compared with conventional ovarian endometrioid carcinomas. Given its association with clear cell features and mismatch repair protein loss, presence of MELF may be useful in clinical decisions regarding surgical staging and Lynch syndrome screening.
Reprod Sci. 2017 Aug;24(8):1121-1128.
Therapeutically Targeting the Inflammasome Product in a Chimeric Model of Endometriosis-Related Surgical Adhesions.
Development of adhesions commonly occurs in association with surgery for endometriosis. Even in the absence of surgery, women with endometriosis appear to be at an enhanced risk of developing adhesions. In the current study, we utilized a chimeric mouse model of experimental endometriosis in order to examine the role of inflammasome activation in the development of postsurgical adhesions. Mice were randomized to receive peritoneal injections of human endometrial tissue fragments or endometrial tissue conditioned media (CM) from women with or without endometriosis 16 hours after ovariectomy and placement of an estradiol-releasing silastic capsule. A subset of mice receiving CM was also treated with interleukin (IL) 1 receptor antagonist (IL-1ra). Our studies demonstrate that peritoneal injection of endometrial tissue fragments near the time of surgery resulted in extensive adhesive disease regardless of tissue origin. However, adhesion scores were significantly higher in mice receiving CM from tissues acquired from patients with endometriosis compared to control tissue CM ( P = .0001). Cytokine bead array analysis of endometrial CM revealed enhanced expression of IL-1β from patients with endometriosis compared to controls ( P < .01). Finally, the ability of human tissue CM to promote adhesive disease was dramatically reduced in mice cotreated with IL-1ra ( P < .0001). Our data implicate enhanced expression of IL-1β in women with endometriosis as a potential causal factor in their increased susceptibility of developing postsurgical adhesions. Thus, targeting inflammasome activation may be an effective strategy for the prevention of surgical adhesions in patients with endometriosis.
Brain Res. 2017 May 15;1663:132-140.
Cannabinoid receptor 1 contributes to sprouted innervation in endometrial ectopic growth through mitogen-activated protein kinase activation.
The endocannabinoid system regulates neurite outgrowth and neurogenesis during development of the central nervous system. Cannabinoid receptor 1 (CB1R) is expressed in neurons, including the somata and fibers, that innervate the endometrial ectopic cyst in rats. Here, we investigated the contribution of CB1R and its downstream signaling to the innervation of endometrial ectopic growth. We found that intrathecal injection of a CB1R agonist enhanced both the density of protein gene product (PGP) 9.5-immunoreactive sprouted nerve fibers and the protein level of PGP 9.5 of the ectopic cyst, and the CB1R antagonist induced opposite effects. The CB1R agonist increased the expression of phosphorylated extracellular signal-regulated kinase (pERK) and c-Jun N-terminal kinase (pJNK), but not pp38, in dorsal root ganglion (DRG), whereas the CB1R antagonist only decreased the expression of pERK. In cultured DRG neurons, CB1R agonists dose-dependently increased neurite elongation. The mitogen-activated protein kinase (MAPK)/ERK kinase (MEK) and JNK inhibitors, but not the p38 inhibitor, attenuated CB1R agonist-induced neurite elongation. The inhibitions of CB1R and its downstream ERK and JNK signaling pathways may alleviate the sprouted innervation that has been involved in ENDO-associated pain. This finding may provide a new therapeutic target for patients with endometriosis.
Immunol Lett. 2017 May;185:52-55.
Interleukin-37 in endometriosis.
Interleukin-37 (IL-37) has been identified as a novel anti-inflammatory cytokine. The present study aimed to evaluate the expression of IL-37 in serum and in peritoneal fluid to determine its clinical significance in endometriosis. Enzyme-linked immunosorbent assay (ELISA) was performed to examine serum IL-37 levels in patients with endometriosis and healthy controls. Peritoneal fluid IL-37 mRNA and NFκB expression were quantified by real-time reverse transcription polymerase chain reaction assays. The association of IL-37 levels with clinical factors and prognosis of endometriosis was analysed. We found that IL-37 levels in PF and in serum were significantly higher in patients with endometriosis compared to women without endometriosis (P=0.0005). IL-37 levels were highly expressed in PF [132.38±34.62pg/mL; P<0.0001] than in serum [74.10±13.49pg/mL] in endometriosis patients. IL-37 mRNA expression contrasted with NFκB mRNA expression in PF from patients with endometriosis. A significant inverse correlation was observed between IL-37 mRNA and NFκB mRNA expression. IL-37 expression correlates with endometriosis severity. The affected NFκB mRNA expression in endometriosiscontributed the to exhibited increase of IL-37. The increased levels of IL-37 may dampen NFκB activation in endometriosis patients.
J Minim Invasive Gynecol. 2017 Jul – Aug;24(5):863-868.
Robotic-Assisted Conservative Excision of Retrocervical-Rectal Deep Infiltrating Endometriosis: A Case Series.
Deep infiltrating endometriosis (DIE) is a complex disease that impairs the quality of life and the fertility of women. Colorectal DIE accounts for 70% to 93% of all the intestinal endometriotic sites and frequently needs a surgical approach. However, the indications for the surgical management of this condition are still controversial. From March 2010 to June 2014, we scheduled 33 consecutive patients presenting with retrocervical-rectal DIE of any diameter not involving the mucosa nor producing rectal stenosis >50% for laparoscopic robotic-assisted nerve-sparing rectal nodulectomy (LRN). All patients were examined preoperatively, at 3 months and 6 months postoperatively, and yearly thereafter. Dysmenorrhea, dyschezia, dyspareunia, and dysuria were evaluated on a 10-point visual analog scale. Among the 33 enrolled patients, 31 (93.9%) fulfilled the selection criteria and were submitted to LRN. In 1 out of 31 available patients (3.2%), a segmental bowel resection was considered necessary for prudential purpose at the end of the nodulectomy procedure. No laparotomic conversion was performed in any case. A wide variety of associated surgical procedures were performed in 25 of 30 patients (83.3%). No intraoperative complications were observed. One grade 3b and 2 grade 1 postoperative complications were recorded. The mean larger axis of the excised nodules measured on the formalin-fixed specimen was 26.4 mm. We found significant improvements in patient symptoms at a 3-month follow-up which persisted over the time. We observed 2 (6.7%) recurrences of intestinal endometriosis and 1 (3.3%) recurrence of chronic pelvic pain without clinical and/or radiologic evidence of endometriotic lesions. The mean follow-up time was 27.6 months. We believe that LRN is feasible and safe and shows promising results in terms of radicality, anatomic recurrence rate, and pain recurrence rate for treating isolated retrocervical-rectal DIE not involving the mucosa, without limiting this procedure to nodules smaller than 3 cm.
Reprod Sci. 2017 Jan 1
Stem Cell Markers Describe a Transition From Somatic to Pluripotent Cell States in a Rat Model of Endometriosis.
To study Thy1 as a fibroblast marker, SSEA1 as a marker of intermediate pluripotency, and Oct4 as a marker of established pluripotency in rat model of endometriosis.
In vivo animal study.
MATERIALS AND METHODS:
Endometriosis was induced in 20 albino female rats through autologous transplantation of one uterine horn to mesentery of intestine. Other 20 rats had their horn removed without transplantation (controls). Rats were sacrificed 4 weeks after induction surgery. Ectopic, eutopic, and control endometria were harvested from endometriosis and control animals respectively. Quantitative syber green based RT-PCR was used to detect expression of Thy-1 (CD90), FUT4 (SSEA1), and POU5F1 (Oct4) genes in tissues. Relative expression was normalized to that of β actin. Thy1, SSEA1, and Oct4 protein expression were detected by immunohistochemistry.
Ectopic endometrium expressed significantly higher mRNA of Oct4 and SSEA1 as compared to control endometrium. Expression levels of Oct4 and SSEA1 were comparable between ectopic and eutopic endometria and between eutopic and control endometria. Thy1 (CD90) gene expression level was comparable among ectopic, eutopic, and control endometria. Oct4 immunoscore were significantly higher in ectopic (6.6±0.91) than eutopic (2.5±0.78) or control endometrium (3.7±0.1) (P value 0.02). Thy1 and SSEA1 immunoscores were comparable among all three types of endometria.
Using rat model of endometriosis, ectopic endometrium showed significantly higher Oct4, and SSEA1, but similar Thy1 gene expression to that of control endometrium. This indicates increased transition from somatic to pluripotent cell states in ectopic endometrium which may play a role in endometriosis pathogenesis.
J Obstet Gynaecol. 2017 Jul;37(5):639-644.
Conservative management in ureteric hydronephrosis due to deep endometriosis: Could the levonorgestrel-intrauterine device be an option?
Endometriosis can affect up to 10% of women of reproductive age, in a wide range of clinical presentations that vary from mild to severe or deep endometriosis. Deep endometriosis can affect the urinary tract in 1-5% to 15-25% cases. Even though deep endometriosis’ surgeries are usually complex with higher rate of complications, conservative management is not always considered as an option because of its high failure rates. This paper describes two cases of deep endometriosis with ureteric involvement (hydronephrosis) treated conservatively with a double-pigtail stent plus a Levonorgestrel intrauterine device, after conservative surgery, who remained symptom free with no evidence of recurrence at 3 years follow-up, avoiding radical high-risk surgery. Impact statement Several treatments have been described for endometriosis. From a symptomatic perspective, conservative medical management has been proposed with a variable response. Concerning deep endometriosis(affecting the urinary or digestive tract), the definitive treatment has always been thought to be radical surgery. However, this can lead to several complications. To illustrate a possible more conservative approach this paper describes two cases of deep infiltrating endometriosis affecting the ureter, treated conservatively with a temporary pigtail ureter stent plus a Levonorgestrel intrauterine device. The management demonstrates that, in a selected population, conservative treatment solves the urinary disease avoiding the surgical complications and, what is more, improving patients’ symptoms in a permanent way. Further prospective studies are needed to confirm whether the introduction of this management in clinical practice would reduce the need for surgery thereby, avoiding high-risk surgery and improving the success rate of conservative management.
Ann Diagn Pathol. 2017 Apr;27:28-33
Seromucinous ovarian tumor A comparison with the rest of ovarian epithelial tumors.
Seromucinous ovarian tumors are rare and not adequately described in the literature and this is especially true for seromucinous carcinomas.
AIM OF THE STUDY:
To describe histological and clinical features of these tumors in comparison with the rest of ovarian epithelial tumors.
MATERIALS AND METHODS:
Two hundred and forty one (241) ovarian tumors, borderline (n=92) or malignant (n=149), treated surgically without neoadjuvant chemotherapy, were examined.
Seromucinous borderline (SMBT) and malignant tumors (SMC) comprised 7.8% (n=7) and 4% (n=6) of all borderline tumors and carcinomas, respectively, studied. Mean age of diagnosis was 63.2 and 68.3years and mean size was 6.4cm and 12cm for SMBT and SMC, respectively. Seromucinous tumors were associated with endometriosis in 23.1% of the cases and they were bilateral in 30.8%. Microscopically, variety in cellular composition, papillary architecture and development into thick walled, occasionally muscular, cysts were the main findings. Medullary/paraovarian/tubal or deeply cortical localization was also characteristic. Stage predicted overall and progression-free survival (p<0.0001 and p=0.03, respectively). Five-year survival was 62% for patients with high grade serous carcinoma, 55% for seromucinous carcinoma, 100% for endometrioid carcinoma, 75% for clear cell carcinoma, and 80% for patients with mucinous carcinoma. Differences were not however statistically significant.
Seromucinous tumors have unique features that support their classification as a different entity. Their localization and their often thick fibrous or/and muscular wall provides further evidence for an histogenesis from the secondary Müllerian system or vestigial structures.
Case Rep Obstet Gynecol. 2017;2017:
Cesarean Scar Endometriosis: An Uncommon Surgical Complication on the Rise? Case Report and Literature Review.
Endometriosis is defined by the presence and growth of ectopic functional endometrial tissue outside the uterus. Scar endometriosis has been described following obstetrical and gynecological surgery. It is a rare condition, though probably on the rise, due to the considerable increase of cesarean sections performed worldwide. Its physiopathology is complex; its symptomatology is rich and diverse but thorough clinical examination along with ultrasound imaging and potentially pretherapeutic cytologic evaluation are usually efficient in diagnosing the condition. Treatment is mostly surgical. We report the case of a cesarean section scar endometriosis, managed at a tertiary level center and emphasize the diagnosis and treatment options.
Ginekol Pol. 2017;88(2):96-102.
Influence of diet on the risk of developing endometriosis.
Endometriosis is a hormone-dependent chronic inflammatory disease characterized by the presence of endometrium beyond the uterine cavity. The disease affects 5-15% of women of child-bearing age, 30-50% of whom suffer from infertility. Understanding the role of dietary factors in the development of endometriosis is critical to development of effective dietary instructions for prevention. Existing studies concerning nutrition and endometriosis suggest that diet is a potentially modifiable risk factor for endometriosis. Fruits and vegetables, fish oils, dairy products rich in calcium and vitamin D, and Omega-3 fatty acids are likely connected with a lower risk of developing endometriosis. Risk factors that increase the risk of endometriosis include consumption of products rich in trans-unsaturated fatty acids, consumption of fats generally, and consumption of beef and other kinds of red meat and alcohol. Currently, there are no clear correlations between par-ticular food products and the risk of endometriosis. Further research is needed in order to fully understand the influence of consumed food products on the risk of development of this disease.
Hum Reprod. 2017 Apr 1;32(4):780-793.
Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis.
Do genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis?
GWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways.
WHAT IS KNOWN ALREADY:
Endometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis.
STUDY DESIGN SIZE, DURATION:
Pathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
The most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software.
MAIN RESULTS AND THE ROLE OF CHANCE:
The first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10-8, OR = 1.71, 95% CI = 1.23-2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10-4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10-5, FDR-P = 3.0 × 10-3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10-4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10-4, FDR-P = 5.0 × 10-4) and with Stage B endometriosis: two overlapping pathways that related to extracellular matrix biology-Core matrisome (P = 1.4 × 10-3, FDR-P = 0.013) and ECM glycoproteins (P = 1.8 × 10-3, FDR-P = 7.1 × 10-3). Genes arising from endometriosis candidate gene studies performed to date were enriched for Interleukin signaling pathway (P = 2.3 × 10-12), Apoptosis signaling pathway (P = 9.7 × 10-9) and Gonadotropin releasing hormone receptor pathway (P = 1.2 × 10-6); however, these pathways did not feature in the results based on GWAS data.
LARGE SCALE DATA:
LIMITATIONS, REASONS FOR CAUTION:
The analysis is restricted to (i) variants in/near genes that can be assigned to pathways, excluding intergenic variants; (ii) the gene-based pathway definition as registered in the databases; (iii) women of European ancestry.
WIDER IMPLICATIONS OF THE FINDINGS:
The top ranked pathways associated with overall and Stage A endometriosis in particular involve integrin-mediated MAPK activation and intracellular ERK/MAPK acting downstream in the MAPK cascade, both acting in the control of cell division, gene expression, cell movement and survival. Other top enriched pathways in Stage B disease include ECM glycoprotein pathways important for extracellular structure and biochemical support. The results highlight the need for increased efforts to understand the functional role of these pathways in endometriosis pathogenesis, including the investigation of the biological effects of the genetic variants on downstream molecular processes in tissue relevant to endometriosis. Additionally, our results offer further support for the hypothesis of at least partially distinct causal pathophysiology for minimal/mild (rAFS I/II) vs. moderate/severe (rAFS III/IV) endometriosis.
STUDY FUNDING/COMPETING INTEREST(S):
The genome-wide association data and Wellcome Trust Case Control Consortium (WTCCC) were generated through funding from the Wellcome Trust (WT084766/Z/08/Z, 076113 and 085475) and the National Health and Medical Research Council (NHMRC) of Australia (241944, 339462, 389927, 389875, 389891, 389892, 389938, 443036, 442915, 442981, 496610, 496739, 552485 and 552498). N.R. was funded by a grant from the Medical Research Council UK (MR/K011480/1). A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant WT098017). All authors declare there are no conflicts of interest.
Hum Reprod. 2017 Apr 1;32(4):770-779
Soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker for diagnosing endometriosis.
Do cell adhesion molecules play a role in endometriosis, and can they be used as a biomarker for diagnosing endometriosis?
Altered expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in the endometrium and peritoneum may play a key role in endometriosis and the soluble VCAM-1/soluble ICAM-1 ratio is a promising biomarker.
WHAT IS KNOWN ALREADY:
Cell adhesion molecules are cell surface proteins that mediate cellular adherence, inflammatory and immune responses, and cancer-related biological processes. Altered expression of VCAM-1 and ICAM-1 in women with endometriosis has been investigated previously; however, gene expression levels in tissues and protein levels in the serum have not been investigated in the same patients.
STUDY DESIGN SIZE, DURATION:
We performed a prospective, longitudinal study (the Endometriosis Marker Austria) in patients who underwent a laparoscopy for benign gynecological pathology in a university-based tertiary referral center for endometriosis. From a total of 138 women who were included in the study from July 2013 through September 2014, 97 had not received hormonal treatment for at least 3 months prior to recruitment and were included in the analysis; 49 (50.5%) of these women had endometriosis, and the 48 (49.5%) who did not have endometriosis served as a control group.
PARTICIPANTS/MATERIALS SETTING METHODS:
During laparoscopy, tissue samples were obtained from ectopic and eutopic endometrium, and from normal pelvic peritoneum. In addition, serum samples were collected immediately before and 6-10 weeks after surgery. The mRNA levels of VCAM-1, ICAM-1 and epithelial cell adhesion molecule (EpCAM) were measured using quantitative real-time PCR, and serum protein levels of soluble VCAM-1 (sVCAM-1), ICAM-1 (sICAM-1) and EpCAM (sEpCAM) were measured using ELISA and correlated with endometriosis status.
MAIN RESULTS AND THE ROLE OF CHANCE:
The mRNA levels of both VCAM-1 and ICAM-1 were higher in ectopic endometriotic lesions than in eutopic endometrium (P < 0.001). Moreover, the mRNA levels of both VCAM-1 and ICAM-1 were higher in normal peritoneum samples obtained from women with endometriosiscompared to those from controls (P = 0.038 and P = 0.009). The mRNA levels of VCAM-1 were also higher in the eutopic endometrium samples obtained from women with endometriosis compared to controls (P = 0.018). With respect to serum protein levels, compared to controls, the women with endometriosis had lower serum levels of sICAM-1 (P = 0.042) and higher levels of sVCAM-1 (P < 0.001). Our analysis revealed that the serum levels of sVCAM-1 were not affected by lesion entity, menstrual cycle phase or disease severity. An receiver operating characteristics curve, calculated to determine whether preoperative serum sVCAM-1 concentration can be used to predict endometriosis, found an AUC of 0.868 with 80% specificity and 84% sensitivity at a cutoff value of 370 pg/ml. This predictive performance can be further improved by calculation of the sVCAM-1/sICAM-1 ratio, leading to an AUC of 0.929 with 86.7% specificity and 90.3% sensitivity at a cutoff ratio value of 1.55.
LARGE SCALE DATA:
LIMITATIONS REASONS FOR CAUTION:
The relatively small sample size in the expression analyses is a possible limitation of this study.
WIDER IMPLICATIONS OF THE FINDINGS:
Our findings could contribute to an improved understanding of the pathogenesis of endometriosis and the role of cell adhesion molecules. In addition, the results may lead to the development of new, non-invasive tools for diagnosing endometriosis. The ability to diagnose patients by measuring serum sVCAM-1 levels or the sVCAM-1/sICAM-1 ratio would have considerable clinical value.
STUDY FUNDING/COMPETING INTEREST(S):
The Ingrid Flick Foundation (Grant no. FA751C0801), which played no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors declare no competing interests.
Hum Reprod. 2017 Apr 1;32(4):719-724.
‘Forever Young’-Testosterone replacement therapy: a blockbuster drug despite flabby evidence and broken promises.
In the last decade, testosterone replacement therapy (TRT) has been increasingly prescribed to treat a controversial condition known as ‘late-onset hypogonadism (LOH)’. This syndrome is diagnosed in men who, for no discernible reason other than older age, obesity or ill health have serum testosterone concentrations below the normal range for healthy young men and report one or more of the following symptoms: muscle weakness or wasting, mood, behaviour and cognition-related symptoms and sexual function or libido impairment. However, recent evidence has demonstrated that testosterone drugs do not substantially ameliorate these symptoms and, more worryingly, that their long-term use may be associated with severe adverse effects (i.e. increased risk of prostate cancer, stroke and myocardial infarction, worsening of benign prostatic hyperplasia symptoms and testicular atrophy). Nonetheless, testosterone drugs have exhibited extraordinary commercial success and their pharmaceutical sales are steadily rising. Behind this apparently unjustifiable trend there are deliberate, well designed direct and indirect pharmaceutical marketing initiatives that exploit the conviction rooted in contemporary society that testosterone can reverse the effects of ageing and ensure social accomplishment. Commercial mechanisms have laid the foundation for disease mongering of LOH and also have resulted a considerable expansion of the indications for treatment. This promotion model deserves particular attention since it is applicable to any drug with a purportedly favourable risk-benefit ratio not supported by evidence.
Hum Reprod Update. 2017 May 1;23(3):276-288.
Surgical treatment of adhesion-related chronic abdominal and pelvic pain after gynaecological and general surgery: a systematic review and meta-analysis.
Chronic pain is a frequent post-operative complication, affecting ~20-40% of patients who have undergone surgery of the female genital or alimentary tract. Chronic pain is an important risk factor for diminished quality of life after surgery. Adhesions are frequently associated with chronic post-operative pain; however, surgical treatment of adhesion-related pain is controversial.
OBJECTIVE AND RATIONALE:
The aim of this study was to investigate the efficacy and harms of surgical interventions for chronic post-operative pain attributable to adhesions.
A search was conducted using PubMed, EMBASE and CENTRAL, without restrictions pertaining to date, publication status or language. Randomized trials and cohort studies from all surgical interventions for chronic post-operative pain were considered eligible. Patients with a concomitant diagnosis that could cause chronic pain (e.g. endometriosis or inflammatory conditions) were excluded. Outcome measures were graded according to clinical relevance, with improvement of pain at long-term follow-up regarded as most clinically relevant.
A total of 4294 unique citations were identified, of which 13 studies met the criteria for inclusion. Two of the analysed studies were randomized trials, of which one had a low risk of bias. Only one trial, randomizing between laparoscopic adhesiolysis without an adhesion barrier and diagnostic laparoscopy, reported improvement of pain at long-term follow-up. In this trial, pain improved in 55.8% of patients after adhesiolysis and in 41.7% of patients in the control group; however, the difference was not significant (relative risk (RR) 1.34; 95% CI: 0.89-2.02). Most non-randomized studies had mid-length follow-up (6-12 months). In pooled analyses of trials and non-randomized studies, improvement of pain was reported in 72% of patients who underwent adhesiolysis (95% CI: 61-83%) at any follow-up longer than 3 months. The incidence of negative laparoscopies was 20% (95% CI: 10-30%). The overall incidence of complications following laparoscopic adhesiolysis was 4% (95% CI: 1-6%).
Laparoscopic adhesiolysis reduces pain from adhesions in ~70% of patients in the initial phase after treatment. However, there is little evidence for long-term efficacy of adhesiolysis for chronic pain. Other drawbacks of laparoscopic adhesiolysis are the high rate of negative laparoscopies and the risk of bowel injury. At present, there is little evidence to support routine use of adhesiolysis in treatment for chronic pain. New research is needed to investigate whether the results of adhesiolysis can be improved with new techniques for diagnosis and prevention of adhesion reformation.
Hum Reprod Update. 2017 May 1;23(3):358-370.
Tubal anastomosis after previous sterilization: a systematic review.
Female sterilization is one of the most common contraceptive methods. A small number of women, however, opt for reversal of sterilization procedures after they experience regret. Procedures can be performed by laparotomy or laparoscopy, with or without robotic assistance. Another commonly utilized alternative is IVF. The choice between surgery and IVF is often influenced by reimbursement politics for that particular geographic location.
OBJECTIVE AND RATIONALE:
We evaluated the fertility outcomes of different surgical methods available for the reversal of female sterilization, compared these to IVF and assessed the prognostic factors for success.
Two search strategies were employed. Firstly, we searched for randomized and non-randomized clinical studies presenting fertility outcomes of sterilization reversal up to July 2016. Data on the following outcomes were collected: pregnancy rate, ectopic pregnancy rate, cost of the procedure and operative time. Eligible study designs included prospective or retrospective studies, randomized controlled trials, cohort studies, case-control studies and case series. No age restriction was applied. Exclusion criteria were patients suffering from tubal infertility from any other reason (e.g. infection, endometriosis and adhesions from previous surgery) and studies including <10 participants. The following factors likely to influence the success of sterilization reversal procedures were then evaluated: female age, BMI and duration and method of sterilization. Secondly, we searched for randomized and non-randomized clinical studies that compared reversal of sterilization to IVF and evaluated them for pregnancy outcomes and cost effectiveness.
We included 37 studies that investigated a total of 10 689 women. No randomized controlled trials were found. Most studies were retrospective cohort studies of a moderate quality. The pooled pregnancy rate after sterilization reversal was 42-69%, with heterogeneity seen from the different methods utilized. The reported ectopic pregnancy rate was 4-8%. The only prognostic factor affecting the chance of conception was female age. The surgical approach (i.e. laparotomy [microscopic], laparoscopy or robotic) had no impact on the outcome, with the exception of the macroscopic laparotomic technique, which had inferior results and is not currently utilized. For older women, IVF could be a more cost-effective alternative for the reversal of sterilization. However, direct comparative data are lacking and a cut-off age cannot be stated.
In sterilized women who suffer regret, surgical tubal re-anastomosis is an effective treatment, especially in younger women. However, there is a need for randomized controlled trials comparing the success rates and costs of surgical reversal with IVF.
Pol Merkur Lekarski. 2017 Mar 21;42(249):121-124.
Intestinal endometriosis – a case report.
Endometriosis intestines due to its non-specific symptoms can pose diagnostic problems, a lack of or incorrect treatment worsens the quality of life, sometimes leading to serious complications. The differential diagnosis of abdominal pain, especially in patients of reproductive age should be taken disease into account. Often abdominal pain in young women are classified as a functional gastrointestinal disorder, and only carefully collected intelligence allows you to focus on the diagnosis of endometriosis, especially if the symptoms significantly impair quality of life.
A CASE REPORT:
A woman 32 year old who was admitted to the department of gastroenterology because of increasing pain in the abdomen. Due to the deteriorating condition of the patient, the characteristics of mechanical obstruction on imaging studies was transferred to the surgical ward with suspected Crohn’s disease. She was treated surgically. Histopathological examination found endometriosis.
Evid Based Complement Alternat Med. 2017
Evaluation of Efficacy and Safety of Dan’e-Fukang Soft Extract in the Treatment of Endometriosis: A Meta-Analysis of 39 Randomized Controlled Trials Enrolling 5442 Patients.
Objective. To systematically evaluate the efficacy and safety of Dan’e-fukang soft extract in endometriosistreatment. Method. PubMed, CNKI, Wanfang Database, VIP, SinoMed, and Cochrane Library were searched. Randomized controlled trials (RCTs) comparing the efficacy of Dan’e-fukang soft extract and conventional western medicines for endometriosis treatment were included. The data were extracted independently by two people and analyzed using RevMan 5.2.0 software. The relative risk (RR) and mean difference (MD) with 95% confidence intervals were considered as effective outcome indicators. Results. Thirty-nine papers including 5442 patients with endometriosis were included in this study. A meta-analysis revealed that Dan’e-fukang soft extract was more efficient than gestrinone in the treatment of endometriosis (RR = 1.08, 95% CI = 1.03 to 1.15, I2 = 71%, REM, 18 trials) and its efficacy was comparable to that of danazol and mifepristone. Dan’e-fukang soft extract was also as effective as gestrinone and mifepristone in terms of relapse rate and relieving dysmenorrhea. The incidence of adverse reactions was lower than that of conventional western medicines. Conclusions. The results of this study showed that Dan’e-fukang soft extract offers certain advantages in endometriosis treatment, but rigorously designed, strictly implemented RCTs are needed to further validate its efficacy.
Pain Physician. 2017 Mar;20(3):185-195.
Comparing the Efficacy of Surgery and Medical Therapy for Pain Management in Endometriosis: A Systematic Review and Meta-analysis.
Pain is considered as one of the main symptoms of endometriosis. The treatment for endometriosis remains controversial.
The aim of this study is to compare the effect of medical or surgical treatments for pain-relief in patients with endometriosis.
Systematic review and meta-analysis.
Published papers about evaluating pain treatment in endometriosis in PubMed, Scopus, and Google Scholar.
After searching all studies evaluating pain treatment in endometriosis in PubMed, Scopus, and Google Scholar, there were 23 related studies, containing 1,847 patients enrolled in our study. We used a variety of tests: fixed and random effects models, Q Cochrane test and I2 index, Egger and Begg tests, forest and funnel plots, Trim and fill method, and meta-regression in our analysis.
There was no statistically significant difference in pain improvement between surgical and medical treatment. Interestingly, pain relief was more prominent longer after treatment. Both clinical trials and cross sectional studies showed higher improvement in pain than cohort studies. High quality studies and lower body mass index (BMI) had a greater effect on pain relief. All studies were heterogeneous, but there was no publication bias.
There was a higher probability of risk of bias in blinding, random sequence generation, and selective outcome reporting in clinical trial studies entered in our meta-analysis.
Our results could not demonstrate the preference of each medical or surgical treatment effect for dysmenorrhea in endometriosis. Additional data is required before a standardized medical protocol can be offered, but we believe this study may encourage clinicians to consider a less invasive alternative for treating their patients’ chronic pelvic pain in the near future.Key words: Endometriosis, pain, meta-analysis, therapy, disease management.
Pain Physician. 2017 Mar;20(3):E451-E454.
Pulsed Radiofrequency Ablation of Pudendal Nerve for Treatment of a Case of Refractory Pelvic Pain.
Pudendal neuralgia (PN) is a result of pudendal nerve entrapment or injury, also called “Alcock syndrome.” Pain that develops is often chronic, and at times debilitating. If conservative measures fail, invasive treatment modalities can be considered. The goal of this case report is to add to a small body of literature that a pulsed radiofrequency (PRF) ablation can be effectively used to treat PN and to show that high resolution MR neurography imaging can be used to detect pudendal neuropathy.
We present a case of a 51-year-old woman with 5 years of worsening right groin and vulva pain. Various medication trials only lead to limited improvement in pain. The first diagnostic right pudendal nerve block was done using 3 mL of 0.25% bupivacaine with 6mg of betamethasone using a transgluteal technique and a target of the right ischial spine; this procedure resulted in ~8 hours of > 50% pain relief. The patient was then referred for MR neurography of the lumbosacral plexus. This study revealed increased signal of the right pudendal nerve at the ischial spine and in the pudendal canal, findings consistent with the clinical picture of PN. Six weeks after the initial block, the patient underwent a second right transgluteal pudendal nerve block, utilizing 3 mL of 0.25% bupivacaine with 40 mg of triamcinolone acetonide; this procedure resulted in ~8 hours of 100% pain relief. Satisfied with these results the patient decided to undergo pudendal nerve PRF ablation for possible long-term relief. For this therapeutic procedure, a right transgluteal approach was again utilized. PRF ablation was performed for 240 seconds at 42° Celsius. Following this ablation the patient reported at least 6 weeks of significant (> 50%) pain relief.
DISCUSSION AND CONCLUSION:
In this paper we presented a case of successful treatment of PN with PRF ablation and detection of pudendal neuropathy on MR neurography. We believe that transgluteal PRF ablation for PN might be an effective, minimally invasive option for those patients that have failed conservative management. MR neurography employed in this case is not only helpful in confirming the diagnosis of PN but could also be useful in ruling out other causes of pelvic pain, such as genitofemoral neuropathy, endometriosis, adenomyosis, or pelvic mass lesion. To conclude, transgluteal PRF ablation can serve as a viable treatment option for mitigating symptoms of pudendal neuropathy and MR neurography is useful in confirming a clinically suspected diagnosis of PN.Key words: Pelvic pain, pudendal neuralgia, MR neurography, pulsed radiofrequency ablation, transgluteal technique, Alcock canal syndrome.
Biol Reprod. 2017 Apr 1;96(4):772-779.
Lipidomic profiling of endometrial fluid in women with ovarian endometriosis†.
The proteomic content of the endometrial fluid (EF) from patients with endometriosis has been investigated, but the lipidomic profile has not been analyzed yet in detail.This study is a comparative untargeted lipidomic analysis of human EF obtained from 35 patients (12 endometriosis and 23 controls). Global differential lipidomic profile was analyzed in both groups by ultrahigh performance liquid chromatography coupled to mass spectrometry. A total of 123 out of the 457 metabolites identified in the EF were found to be significantly differentially expressed between ovarian endometriosis (OE) versus controls. Univariate statistical analysis showed reduced levels of saturated diacylglycerols and saturated triacylglycerols in endometriosis patients. A predictive model was generated using the 123 differentially expressed metabolites. Using this model, we were able to correctly classify 86% of the samples. This study identified the lipidomic profile in the EF associated with OE, suggesting that EF analysis could be considered as a minimally invasive approach for the diagnosis of endometriosis. In conclusion, the lipidomic profile of the EF is different between samples from patients with OE and controls.
Eur J Obstet Gynecol Reprod Biol. 2017 May;212:69-74.
Value of the 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. A pilot study.
The non-invasive diagnosis of endometriosis remains challenging. Recent data suggested that somatostatin might be involved in its pathogenesis. High sensitive visualization of somatostatin receptors expression is possible using PET-CT imaging after the administration of a 68Ga-labeled somatostatin analog (DOTATATE) that will bind to the somatostatin receptor sub-types 2 and 5. The aim of the present study was to assess the usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis.
This is a prospective, single center pilot study. A pre operative 68Ga-DOTATATE PET-CT was performed in all of the patients who presented with suspected endometriosis and who were scheduled for a laparoscopy. Surgical endometriosis staging and histopathological analysis, including somatostatin receptors SST1, 2 and 5 immunohistochemistry (IHC) of removed specimens, were confronted to the results of the 68Ga-DOTATATE PET-CT.
12 patients were included in this study. 68Ga-DOTATATE PET-CT performed pre operatively showed increased pathologic uptake in four patients with a deep infiltrating endometriosis (DIE) recto-vaginal lesion and in another patient with an adenomyoma. Expression of SST1, 2 and 5 receptors in surgical specimens was confirmed by IHC in these five lesions. Neither superficial peritoneal endometriosis, nor ovarian endometrioma were found to show an increased pathologic uptake on 68Ga-DOTATATE PET-CT. IHC analysis confirmed that SST1, 2, and 5 receptors were not present in these lesions.
The results observed in this small size series of patients seem to confirm expression of somatostatin receptors only in recto-vaginal DIE and focal adenomyosis lesions. The usefulness of 68Ga-DOTATATE PET-CT in the diagnosis of this entity is uncertain. Future research should concentrate on studying the role of somatostatin in the pathogenesis of DIE.
Obstet Gynecol Sci. 2017 Mar;60(2):236-239.
Catamenial hemoptysis accompanied by subcutaneous endometriosis treated with combination therapy.
Extra pelvic endometriosis is considered to be rare. This paper reports a case of catamenial hemoptysis accompanied by subcutaneous endometriosis in 26-year-old woman. A computed tomography scan of the chest revealed a focal ground-glass opacity lesion in the posterior segment of the right upper lobe. Histopathology confirmed the diagnosis of endometriosis of right lung and concurrent subcutaneous endometriosis. She was treated with surgical resection of the endometriosis lesions on two different sites and perioperative gonadotropin-releasing hormone agonist therapy. The 6-month follow-up after combination treatment showed no recurrence. Though long-term follow-up result is needed, aggressive treatment using combination treatment (surgery and perioperative medication) should be considered for symptomatic extra pelvic endometriosis.
Reprod Sci. 2017 Dec;24(12):1577-1582.
Deep Infiltrating Endometriosis and Endometrial Adenocarcinoma Express High Levels of Myostatin and Its Receptors Messenger RNAs.
Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions. Endometrial specimens were collected by hysteroscopy, whereas endometriotic lesions were collected by laparoscopy, and adenocarcinomas were sampled after hysterectomy. Total RNA was extracted from tissue homogenates, and gene expression was assessed by quantitative real-time polymerase chain reaction. Myostatin and myostatin receptors mRNAs were expressed by healthy endometrium throughout the menstrual cycle, with no differences between the proliferative and secretory phase. The highest myostatin mRNA expression was found in patients with deep infiltrating endometriosis (DIE) and in endometrial carcinoma; expression was also found in ovarian endometrioma (OMA ) and endometrial polyps. Myostatin receptors mRNA expression was higher in DIE and adenocarcinomas compared to control endometrium. The expression of ALK5 and ActRIIB in OMA was higher than in controls, whereas polyps had an increased expression of ALK5 mRNA. In conclusion, the present data showed for the first time the expression of myostatin in healthy endometrium and a higher expression in endometriosis and endometrial cancer, suggesting myostatin involvement in human endometrial physiology and related pathologies.
Exp Biol Med (Maywood). 2017 Apr;242(8):884-895
Lymphangiogenesis: fuel, smoke, or extinguisher of inflammation’s fire?
Lymphangiogenesis is a recognized hallmark of inflammatory processes in tissues and organs as diverse as the skin, heart, bowel, and airways. In clinical and animal models wherein the signaling processes of lymphangiogenesis are manipulated, most studies demonstrate that an expanded lymphatic vasculature is necessary for the resolution of inflammation. The fundamental roles that lymphatics play in fluid clearance and immune cell trafficking from the periphery make these results seemingly obvious as a mechanism of alleviating locally inflamed environments: the lymphatics are simply providing a drain. Depending on the tissue site, lymphangiogenic mechanism, or induction timeframe, however, evidence shows that inflammation-associated lymphangiogenesis (IAL) may worsen the pathology. Recent studies have identified lymphatic endothelial cells themselves to be local regulators of immune cell activity and its consequential phenotypes – a more active role in inflammation regulation than previously thought. Indeed, results focusing on the immunocentric roles of peripheral lymphatic function have revealed that the basic drainage task of lymphatic vessels is a complex balance of locally processed and transported antigens as well as interstitial cytokine and immune cell signaling: an interplay that likely defines the function of IAL. This review will summarize the latest findings on how IAL impacts a series of disease states in various tissues in both preclinical models and clinical studies. This discussion will serve to highlight some emerging areas of lymphatic research in an attempt to answer the question relevant to an array of scientists and clinicians of whether IAL helps to fuel or extinguish inflammation. Impact statement Inflammatory progression is present in acute and chronic tissue pathologies throughout the body. Lymphatic vessels play physiological roles relevant to all medical fields as important regulators of fluid balance, immune cell trafficking, and immune identity. Lymphangiogenesis is often concurrent with inflammation and can potentially aide or worsen disease progression. How new lymphatic vessels impact inflammation and by which mechanism is an important consideration in current and future clinical therapies targeting inflammation and/or vasculogenesis. This review identifies, across a range of tissue-specific pathologies, the current understanding of inflammation-associated lymphangiogenesis in the progression or resolution of inflammation.
Gynecol Endocrinol. 2017 Jul;33(7):544-547
Endometriosis doubles the risk of sexual dysfunction: a cross-sectional study in a large amount of patients.
Endometriosis affects several aspects of a woman’s life, including sexual function, but which specific aspects of sexual function remains unclear.
A cross-sectional study was performed involving 1001 women divided into two groups, according to the presence or absence of endometriosis. We assessed sexual function, anxiety and depression of patients and correlated these findings with symptoms, locations and types of endometriosis and the affected domains of sexual function. Eighteen completed the forms incorrectly, 294 women (29.9%) were excluded due to severe anxiety and depression. One hundred and six patients had symptoms that could have any relation to endometriosis, so they were also excluded. The final cohort was composed of 254 patients with endometriosis and 329 patients without the disease. Sexual function score was assessed using the female sexual quotient (FSQ); Beck inventories were used to assess anxiety and depression.
Patients with endometriosis were affected in all phases of sexual response: desire, sexual arousal, genital-pelvic pain/ penetration and orgasm/ sexual satisfaction. In the overall assessment, 43.3% of patients with endometriosis had sexual dysfunction, while the population without endometriosis sexual dysfunction occurred in 17.6% of women.
Patients with endometriosis have more than twice sexual dysfunctions as compared to women without the disease.
Reproduction. 2017 Jun;153(6):809-820.
Hypoxia-inducible factor-1α promotes endometrial stromal cells migration and invasion by upregulating autophagy in endometriosis.
Endometriosis is a benign gynecological disease that shares some characteristics with malignancy like migration and invasion. It has been reported that both hypoxia-inducible factor-1α (HIF-1α) and autophagy were upregulated in ectopic endometrium of patients with ovarian endometriosis. However, the crosstalk between HIF-1α and autophagy in the pathogenesis of endometriosis remains to be clarified. Accordingly, we investigated whether autophagy was regulated by HIF-1α, as well as whether the effect of HIF-1α on cell migration and invasion is mediated through autophagy upregulation. Here, we found that ectopic endometrium from patients with endometriosis highly expressed HIF-1α and autophagy-related protein LC3. In cultured human endometrial stromal cells (HESCs), autophagy was induced by hypoxia in a time-dependent manner and autophagy activation was dependent on HIF-1α. In addition, migration and invasion ability of HESCs were enhanced by hypoxia treatment, whereas knockdown of HIF-1α attenuated this effect. Furthermore, inhibiting autophagy with specific inhibitors and Beclin1 siRNA attenuated hypoxia triggered migration and invasion of HESCs. Taken together, these results suggest that HIF-1α promotes HESCs invasion and metastasis by upregulating autophagy. Thus, autophagy may be involved in the pathogenesis of endometriosis and inhibition of autophagy might be a novel therapeutic approach to the treatment of endometriosis.
Aust N Z J Obstet Gynaecol. 2017 Aug;57(4):452-457.
Endometriosis education in schools: A New Zealand model examining the impact of an education program in schools on early recognition of symptoms suggesting endometriosis.
Menstrual morbidity plays a significant role in adolescent females’ lives. There are no studies to date reporting such data from menstrual health education programs in schools.
The aim of our study was to report results from an audit of a menstrual health and endometriosis education program in secondary schools and observe age patterns of young women presenting for menstrual morbidity care.
MATERIALS AND METHODS:
Audit data from education in secondary schools and audit data of patients from an Endometriosis and Pelvic Pain Coaching clinic operating in a private endometriosis specialised centre are reported.
In a region of consistent delivery of the education program, student awareness of endometriosis was 32% in 2015. Overall in 2015, 13% of students experienced distressing menstrual symptoms and 27% of students sometimes or always missed school due to menstrual symptoms. Further, in one region of consistent delivery of the menstrual health education program, data show an increase in younger patients attending for specialised endometriosis care.
There is strong suggestive evidence that consistent delivery of a menstrual health education program in schools increases adolescent student awareness of endometriosis. In addition, there is suggestive evidence that in a geographical area of consistent delivery of the program, a shift in earlier presentation of young women to a specialised health service is observed.
Gynecol Obstet Invest. 2017;82(4):313-321.
Decidual Bleeding as a Cause of Spontaneous Hemoperitoneum in Pregnancy and Risk of Preterm Birth.
Spontaneous hemoperitoneum in pregnancy (SHiP) is a rare, life-threatening event, particularly relevant to women with endometriosis or deciduosis.
To determine the type of lesions leading to SHiP, a literature search was conducted among all published SHiP cases. From a total of 1,339 publications, information on pathological findings at the bleeding site with histological data was found in 24 case reports (16 pregnant, 8 postpartum).
Among pregnant women (81% primigravida), 75% had a diagnosis of endometriosis and 25% of deciduosis. Among postpartum women (38% primiparous), 63% had a diagnosis of deciduosis and 25% of endometriosis. In all cases except one, decidual cells, with or without glandular structures, were present at the bleeding site. Decidual vessels were described in 7 cases and all exhibited vascular changes, including distension of the lumen, medial disorganization, or loss of vascular integrity. These vessels were significantly different from arteries seen in the secretory endometrium, showing that structural modifications take place during the initial stage of the remodelling of placental bed spiral arteries.
During pregnancy, a link seems to exist between ectopic decidualization, particularly that occurring in endometriotic foci, and occurrence of SHiP. In addition, subclinical decidual bleeding may be a potential risk factor for preterm labour.
Abdominal Wall Endometriosis in a Rhesus Macaque (Macaca mulatta).
Endometriosis is the presence of endometrium outside of the uterus. Although endometriosis occurs in both pelvic and extrapelvic locations, extrapelvic locations are less common. The development of abdominal wall or incisional endometriosis in women is associated with gynecologic surgeries and is often misdiagnosed. Because they naturally develop endometriosis similar to women,Old World NHP, including rhesus macaques, provide excellent opportunities for studying endometriosis. Here, we describe a case of abdominal wall endometriosis in a rhesus macaque that had undergone cesarean section. Microscopically, the tissue consisted of pseudocolumnar epithelium-lined glands within a decidualized stroma, which dissected through the abdominal wall musculature and into the adjacent subcutaneous tissue. The stroma was strongly positive for vimentin and CD10 but was rarely, weakly positive for estrogen receptors and negative for progesterone. Close examination of extrapelvic endometriosis in rhesus macaques and other NHP may promote increased understanding of endometriosis in women.
Zhonghua Fu Chan Ke Za Zhi. 2017 Mar 25;52(3):164-167.
Clinical analysis of pelvic abscess with endometriosis.
Objective: To investigate the clinical features, diagnosis and treatments of pelvic abscess with endometriosis. Methods: A retrospective analysis was performed on 129 cases of pelvic abscess in Peking Union Medical College Hospital from January 2000 to January 2016. Among them, 34 women with endometriosis were divided into the study group and the others were in the control group. The clinical characteristics, therapeutic regimens and outcomes were compared. Results: (1) General conditions: there were no statistic differences between the two groups in age, WBC, serum CA(125), intrauterine device in use, pelvic inflammatory disease history; while incidence rates of dysmenorrhea (65%, 22/34) and infertility (21%, 7/34) in the study group were higher than those in the control group (all P<0.05). (2) Clinical manifestations: fever, abdominal pain and pelvic mass were the main symptoms in two groups. The incidence rates of septic shock were 12% (4/34) in the study group and 2% (2/95) in the control group (P<0.05). (3) Treatment: treatment with puncture all failed in the study group (7/7) and surgeries were required. In contrast, there was only 1/19 treatment failure with puncture in the control group. The puncture failure rates were statistically significant (P<0.05). Compared with the study group and the control group, there were significant differences (P<0.05) in the operation time of laparoscopic surgery [(76±41) versus (53±21) minutes] and of laparotomy [(168±58) versus (116±35) minutes], intra-operative blood loss of laparoscopic surgery [(216±296) versus (43±36) ml] and of laparotomy [(448±431) versus (145±24) ml]. Conclusions: Pelvic abscess in women with endometriosis is more severe and refractory to antibiotics and puncture treatment. Active surgical intervention is required. Although surgical procedures are often difficult, prognosis is comparatively satisfied.
Int J Womens Health. 2017 Mar 23;9:157-161
Robotic-assisted hysterectomy: patient selection and perspectives.
Minimally invasive hysterectomy via the laparoscopic or vaginal approach is beneficial to patients when compared with laparotomy, but has not been offered in the past to all women because of the technical difficulties and the long learning curve required for laparoscopic hysterectomy. Robotic-assisted hysterectomy for benign indications may allow for a shorter learning curve but does not offer clear advantages over conventional laparoscopic hysterectomy in terms of surgical outcomes. In addition, robotic hysterectomy is invariably associated with increased costs. Nevertheless, this surgical approach has been widely adopted by gynecologic surgeons. The aim of this review is to describe specific indications and patients who may benefit from robotic-assisted hysterectomy. These include hysterectomy for benign conditions in cases with high surgical complexity (such as pelvic adhesive disease and endometriosis), hysterectomy and lymphadenectomy for treatment of endometrial carcinoma, and obese patients. In the future, additional evidence regarding the benefits of single-site robotic hysterectomy may further modify the indications for robotic-assisted hysterectomy.
J Affect Disord. 2017 Aug 1;217:34-41
Preconception gynecological risk factors of postpartum depression among Japanese women: The Japan Environment and Children’s Study (JECS).
Postpartum depression is one of the major causes of disability among women who are on their childbearing years. Identifying people at risk of postpartum depression may improve its management. The objective of this study was to determine the probable association between postpartum depression and some preconception gynecological morbidities.
Data from a nationwide birth cohort study, the Japan Environment and Children’s study (JECS), up to one month of postpartum were analyzed. To assess postpartum depression, the Edinburgh Postnatal Depression Scale (EPDS) was used; 11 preconception gynecological morbidities were considered as risk factors. Covariates included psychiatric illness history, psychosocial factors, some pregnancy adverse outcomes, birth outcomes, socio-demographic and health behavioral factors.
Except for the prevalence of previous miscarriage, leiomyoma and polycystic ovarian syndrome, depressive women had more gynecological morbidities compared to non-depressive ones. In logistic regression model, endometriosis (OR, 1.27; 95%CI: 1.15-1.41), dysmenorrhea (OR, 1.13; 95%CI: 1.06-1.21) and abnormal uterine bleeding (OR, 1.21; 95%CI: 1.15-1.29) were associated with postpartum depression.
CONCLUSION: Women with endometriosis and menstrual problems were at risk of developing postpartum depression. This study suggests a perinatal mental health screening for predisposed women.
Fertil Steril. 2017 Apr;107(4):969-976.
Spontaneous fertility after expectant or surgical management of rectovaginal endometriosis in women with or without ovarian endometrioma: a retrospective analysis.
To investigate spontaneous pregnancy rate (SPRs) of women with rectovaginal endometriosis (RV) with/without ovarian endometrioma (OMA) and treated with the use of expectant or surgical management.
The study included patients with RV with or without OMA who tried to conceive spontaneously for 1 year either without undergoing surgery (group E; n = 284) or after surgery (group S; n = 221). The study population was further divided into four subgroups: women with RV without OMA who directly tried to conceive (group eRV; n = 121) or tried to conceive after surgery (group sRV; n = 96), and women with RV with OMA who directly tried to conceive (group eOMA; n = 163) or tried to conceive after surgery (group sOMA; n = 125).
Expectant or surgical management.
MAIN OUTCOME MEASURE(S):
Crude and cumulative SPRs.
At 1 year, crude and cumulative SPRs were lower in group E (17.3% and 23.8%, respectively) than in group S (35.7% and 39.5%). Similarly, crude and cumulative SPRs were lower in group eRV (24.8% and 30.6%) than in group sRV (42.7% and 45.7%, respectively) and in group eOMA (11.7% and 18.0%) than group sOMA (30.4% and 34.5%). At 1 year, crude and cumulative SPRs were higher in group eRV (24.8% and 30.6%) than in group eOMA (11.7% and 18.0%), and in group sRV (42.7% and 45.7%) than in group sOMA (30.4% and 34.5%).
Crude and cumulative SPRs are lower in women treated with the use of expectant rather than surgical management. The presence of OMAs decreases SPRs independently from the treatment modality adopted.
Case Rep Neurol Med. 2017;2017
Sacral Neuromodulation: Foray into Chronic Pelvic Pain in End Stage Endometriosis.
Excision of all endometriotic lesions is the method of choice in the treatment of severe endometriosis resistant to medical therapy. The infiltrating nature of the disease as well as extensive surgery may, however, cause chronic pain that cannot be relieved by either surgery or hormonal treatment. As a pilot treatment, we tested the effect of sacral neuromodulation (SNM) for four endometriosis patients suffering chronic pelvic pain and pelvic organ dysfunction after radical surgical treatment. Three out of four patients reported improvement in their symptoms during the neuromodulation testing period and a permanent pulse generator was installed. After 2.5 years, all three patients report better quality of life and want to continue with SNM.
Cell J. 2017 Apr-Jun;19(1):50-64.
Lovastatin Reduces Stemness via Epigenetic Reprograming of BMP2 and GATA2 in Human Endometrium and Endometriosis.
The stem cell theory in the endometriosis provides an advanced avenue of targeting these cells as a novel therapy to eliminate endometriosis. In this regard, studies showed that lovastatin alters the cells from a stem-like state to more differentiated condition and reduces stemness. The aim of this study was to investigate whether lovastatin treatment could influence expression and methylation patterns of genes regulating differentiation of endometrial mesenchymal stem cells (eMSCs) such as BMP2, GATA2 and RUNX2 as well as eMSCs markers.
MATERIALS AND METHODS:
In this experimental investigation, MSCs were isolated from endometrial and endometriotic tissues and treated with lovastatin and decitabin. To investigate the osteogenic and adipogenic differentiation of eMSCs treated with the different concentration of lovastatin and decitabin, BMP2, RUNX2 and GATA2 expressions were measured by real-time polymerase chain reaction (PCR). To determine involvement of DNA methylation in BMP2 and GATA2 gene regulations of eMSCs, we used quantitative Methylation Specific PCR (qMSP) for evaluation of the BMP2 promoter status and differentially methylated region of GATA2 exon 4.
In the present study, treatment with lovastatin increased expression of BMP2 and RUNX2 and induced BMP2 promoter demethylation. We also demonstrated that lovastatin treatment down-regulated GATA2expression via inducing methylation. In addition, the results indicated that CD146 cell marker was decreased to 53% in response to lovastatin treatment compared to untreated group.
These findings indicated that lovastatin treatment could increase the differentiation of eMSCs toward osteogenic and adiogenic lineages, while it decreased expression of eMSCs markers and subsequently reduced the stemness.
Gynecol Oncol Rep. 2017 Mar 14;20:78-80.
Clear cell carcinoma arising from abdominal wall endometriosis – Brief report and review of the literature.
- Endometriosis-associated abdominal wall cancer is a rare entity with poor prognosis.•Personal history of C-section is extremely relevant.•The treatment consists in a wide local excision with adjuvant chemotherapy.•Proper treatment of abdominal endometriosiscould prevent these situations.