Oncotarget. 2017 Mar 22;8(40):66951-66959.

Upregulation of CFTR in patients with endometriosis and its involvement in NFκB-uPAR dependent cell migration.

Huang W^#1,2, Jin A^#3, Zhang J^#1,2, Wang C^1,2, Tsang LL^1,2, Cai Z³, Zhou X³, Chen H^1,2, Chan HC^1,2,4.

 

Abstract

Endometriotic tissues exhibit high migration ability with the underlying mechanisms remain elusive. Our previous studies have demonstrated that cystic fibrosis transmembrane conductance regulator (CFTR) acts as a tumor suppressor regulating cell migration. In the present study, we explored whether CFTR plays a role in the development of human endometriosis. We found that both mRNA and protein expression levels of CFTR and urokinase-type plasminogen activator receptor (uPAR) were significantly increased in ectopic endometrial tissues from patients with endometriosis compared to normal endometrial tissues from women without endometriosis and positively correlated. In human endometrial Ishikawa (ISK) cells, overexpression of CFTR stimulated cell migration with upregulated NFκB p65 and uPAR. Knockdown of CFTR inhibited cell migration. Furthermore, inhibition of NFκB with its inhibitors (curcumin or Bay) significantly reduced the expression of uPAR and cell migration in the CFTR-overexpressing ISK cells. Collectively, the present results suggest that the CFTR-NFκB-uPAR signaling may contribute to the progression of human endometriosis, and indicate potential targets for diagnosis and treatment.

 

 

 

F1000Res. 2017 Sep 7;6:1657.

Single-incision laparoscopic surgery in gynecologic surgery: a single-institutional experience from Saudi Arabia.

Salamah K¹, Abuzaid M¹, Abu-Zaid A^2,3.

 

Abstract

Background: Laparoscopy is rapidly replacing laparotomy in the field of gynecologic surgery. Generally, there are limited data concerning the utility of single-incision laparoscopic surgery (SILS) in gynecologic surgery. Specifically, in Saudi Arabia, a third-world country, data are further limited; only one related study has been conducted so far. The purpose of this study is to retrospectively report our single-institutional experience of SILS in terms of feasibility, safety and perioperative outcomes in the management of various gynecologic conditions. Methods: The study took place at the Women’s Specialized Hospital, King Fahad Medical City, Riyadh, Saudi Arabia. From January 2012 to May 2016, all gynecologic patients who underwent SILS procedures were analyzed for pre-, intra- and post-operative details. SILS was performed using a single multi-port trocar and standard laparoscopic instruments. Results: A total of 54 patients underwent 66 SILS procedures. The median age and body mass index (BMI) were 36 years and 28.2 kg/m ², respectively. Fourteen patients (26%) had ≥ 1 previous abdominal and/or pelvic surgeries. Twenty-four patients (44.4%) were nulliparous. The three most commonly performed SILS procedures were unilateral salpingo-oophorectomy (45.5%) and unilateral ovarian cystectomy (27.3%) and adhesiolysis (6.1%). The median operative time, estimated blood loss and hospital stay were 74 min, 50 ml and 1 day, respectively. Three patients required conversion to laparotomy, as follows: unidentified non-stopping bleeding source (n=1) and endometriosis stage IV resulting in difficult dissection (n=2). One patient developed post-operative incisional hernia that was treated surgically. The median patients’ post-operative pain (according to Wong-Baker FACES Foundation pain rating scale) within 4 hours was 2. At 4-week post-operatively, the median wound scar length (measured at outpatient clinic) was 2 cm. Conclusions: SILS is feasible, safe and associated with acceptable clinical and surgical outcomes.

 

 

 

Insights Imaging. 2017 Dec;8(6):549-556.

MRI for adenomyosis: a pictorial review.

Agostinho L¹, Cruz R², Osório F³, Alves J³, Setúbal A³, Guerra A⁴.

Abstract

Adenomyosis is defined as the presence of ectopic endometrial glands and stroma within the myometrium. It is a disease of the inner myometrium and results from infiltration of the basal endometrium into the underlying myometrium. Transvaginal ultrasonography (TVUS) and magnetic resonance imaging (MRI) are the main radiologic tools for this condition. A thickness of the junctional zone of at least 12 mm is the most frequent MRI criterion in establishing the presence of adenomyosis. Adenomyosis can appear as a diffuse or focal form. Adenomyosis is often associated with hormone-dependent lesions such as leiomyoma, deep pelvic endometriosis and endometrial hyperplasia/polyps. Herein, we illustrate the MRI findings of adenomyosis and associated conditions, focusing on their imaging pitfalls.

TEACHING POINTS:

• Adenomyosis is defined as the presence of ectopic endometrium within the myometrium. • MRI is an accurate tool for the diagnosis of adenomyosis and associated conditions. • Adenomyosis can be diffuse or focal. • The most established MRI finding is thickening of junctional zone exceeding 12 mm. • High-signal intensity myometrial foci on T2- or T1-weighted images are also characteristic.

 

 

 

Int J Gynaecol Obstet. 2018 Jan;140(1):11-17.

Systematic review and meta-analysis of the effect of bipolar electrocoagulation during laparoscopic ovarian endometrioma stripping on ovarian reserve.

Deckers P¹, Ribeiro SC¹, Simões RDS¹, Miyahara CBDF¹, Baracat EC¹.

Abstract

BACKGROUND:

Laparoscopic stripping is the gold-standard treatment for ovarian endometriosis. The choice of hemostasis method might affect ovarian reserve.

OBJECTIVES:

To determine whether bipolar electrocoagulation is more detrimental to ovarian reserve than non-thermal hemostasis methods.

SEARCH STRATEGY:

Entry terms associated with the MeSH terms “endometrioma,” “laparoscopy,” and “ovarian reserve” were used to search databases for articles published up to April 3, 2017, in English, Spanish, Portuguese, French, and Italian.

SELECTION CRITERIA:

Randomized controlled trials comparing the 3-month postoperative serum anti-Müllerian hormone (AMH) level in premenopausal women undergoing laparoscopic stripping with bipolar hemostasis or non-thermal hemostasis methods were selected.

DATA COLLECTION AND ANALYSIS:

Data were extracted by two independent reviewers and a meta-analysis was performed.

MAIN RESULTS:

Three studies met the inclusion criteria; overall, 105 patients underwent surgery with bipolar electrocoagulation and 105 patients underwent surgery with an alternative hemostasis method. The AMH level 3 months after surgery was decreased in the bipolar electrocoagulation group (mean difference -0.79 ng/mL, 95% confidence interval -1.19 to -0.39).

CONCLUSIONS:

Bipolar electrocoagulation negatively impacts ovarian reserve and should be avoided, especially for patients with reproductive goals.

 

 

Acta Obstet Gynecol Scand. 2017 Dec;96(12):1446-1452.

The menstrual cycle and blood loss during laparoscopic myomectomy.

Clark NV¹, Wang KC¹, Opoku-Anane J¹, Hill-Lydecker CI¹, Vitonis AF¹, Einarsson JI¹, Cohen SL¹.

Abstract

INTRODUCTION:

Operative morbidity of laparoscopic myomectomy largely relates to the potential for intraoperative blood loss. We sought to determine whether blood loss varies according to the menstrual cycle.

MATERIAL AND METHODS:

A retrospective study of 268 women who underwent a laparoscopic myomectomy from 2007 to 2012. Patients were categorized into five menstrual groups: follicular phase, luteal phase, oligomenorrheic or amenorrheic on hormonal therapy, postmenopausal or other. Patient and procedure characteristics were compared for the follicular phase group, luteal phase group, and hormonal therapy group. The estimated blood loss was compared across the five groups using a regression model.

RESULTS:

A total of 268 women underwent a laparoscopic myomectomy: 108 (40.3%) were in the follicular phase, 92 (34.3%) were in the luteal phase, 44 (16.4%) were on hormonal therapy, nine (3.4%) were postmenopausal, and 15 (5.6%) could not be classified. Baseline patient characteristics were similar between the groups with the exception of endometriosis. Geometric mean estimated blood loss was 91.9 mL in the follicular phase group, 108.7 mL in the luteal phase group, 114.1 mL in the hormonal therapy group, and 39.8 mL in the postmenopausal group. There was no significant difference in the geometric mean estimated blood loss when comparing the follilcuar phase, luteal phase, and hormonal phase groups (p = 0.41). Upon adjusted multivariable analysis of all five menstrual groups, there was also no difference in estimated blood loss.

CONCLUSIONS:

Intraoperative blood loss during laparoscopic myomectomy does not vary significantly with the phase of the menstrual cycle.

 

 

 

 

 

 

Reprod Sci. 2017 Jan 1:1933719117732165.

The Effect of Copper on Endometrial Receptivity and Induction of Apoptosis on Decidualized Human Endometrial Stromal Cells.

Carrascosa JP¹, Cotán D¹, Jurado I¹, Oropesa-Ávila M^2,3, Sánchez-Martín P⁴, Savaris RF⁵, Tan J⁶, Sánchez-Alcázar JA^2,3, Tan SL^7,8, Horcajadas JA^9,10.

 

Abstract

Intrauterine devices (IUDs) have been widely used to prevent pregnancies with great efficacy during decades. It has been demonstrated that IUD alters the endometrial gene expression, but there is no scientific data about how copper, a metal commonly used in these devices, by itself, is able to influence the processes of endometrial receptivity and apoptosis in decidualized human endometrial stromal cells. Five endometrial samples were obtained from fertile women and processed by a standard protocol to obtain human endometrial stromal cells for in vitro studies. Stromal cells were cultured in vitro and decidualized for 8 days. At day 6, copper was added to the treatment group or camptothecin as positive control for apoptosis until day 8. Five endometrial samples were used in each group. The aim of this study was to analyze the effect of copper in apoptosis and necrosis by flow cytometry, to visualize the apoptotic microtubule network during apoptosis by immunofluorescence, and finally to determine the gene expression profile of a panel of 192 genes related to endometrial receptivity and immune system by quantitative reverse transcription PCR (RT-qPCR). Copper, compared to the decidualized group, induced changes in the gene expression by an order of magnitude in 49 genes (42 up- and 9 downregulated). This alteration in the decidualization gene signature by copper includes 19 genes involved in the endometriosispathology and others related to other gynecological disorders such as preeclampsia and infertility. Our results indicate that copper does not increase the apoptosis level induced by the decidualization treatment. However, copper alters the gene expression of some biomarkers of endometrial receptivity and immune response.

 

 

 

Am J Surg Pathol. 2018 Feb;42(2):227-233.

Targeted Genomic Profiling Reveals Recurrent KRAS Mutations in Mesonephric-like Adenocarcinomas of the Female Genital Tract.

Mirkovic J¹, McFarland M², Garcia E³, Sholl LM³, Lindeman N³, MacConaill L^3,4, Dong F³, Hirsch M⁵, Nucci MR⁵, Quick CM⁶, Crum CP⁵, McCluggage WG², Howitt BE⁵.

 

Abstract

Mesonephric adenocarcinoma most commonly arises in the cervix and is presumed to be derived from normal or hyperplastic mesonephric remnants. It is characterized by recurrent KRAS mutations and lack of PIK3CA/PTEN alterations. Adenocarcinomas of the uterine corpus and ovary characterized by morphologic and immunophenotypic similarities to mesonephric adenocarcinoma have been reported. The pathogenesis of these tumors, which have been designated “mesonephric-like adenocarcinomas” is unknown, and it has been debated whether these represent mesonephric adenocarcinomas that arise in the endometrium/ovary or endometrioid adenocarcinomas that closely mimic mesonephric adenocarcinoma. The relationship at the molecular level between mesonephric adenocarcinomas and mesonephric-like adenocarcinomas is unknown. The aim of this study was to examine the molecular alterations in mesonephric-like adenocarcinomas to identify driver mutations and potential therapeutically targetable mutations, and to determine the relationship between mesonephric-like adenocarcinomas and mesonephric adenocarcinomas using targeted next-generation sequencing. Seven mesonephric-like adenocarcinomas (4 ovarian, 3 uterine corpus) underwent targeted next-generation sequencing to detect mutations, copy number variations and structural variants in exonic regions of 300 cancer genes, and 113 selected intronic regions across 35 genes. All 7 tumors (100%) harbored canonical activating KRAS mutations (4 G12D, 3 G12V). PIK3CA activating mutations were identified in 3 of 7 (43%) cases. There were no alterations in PTEN, ARID1A, or TP53 in any of the tumors. In copy number analysis, 5 of 7 (71%) tumors exhibited 1q gain, which was accompanied by 1p loss in 2 cases. In addition, 4 of 7 (57%) tumors had chromosome 10 gain, which was accompanied by gain of chromosome 12 in 3 cases. Mesonephric-like adenocarcinomas, similar to mesonephric adenocarcinomas, are characterized by recurrent KRAS mutations, gain of 1q, lack of PTEN mutations, and gains of chromosomes 10 and 12. PIK3CA mutations, which have not previously been identified in mesonephric adenocarcinoma, were found in 3 of 7 (43%) mesonephric-like adenocarcinomas in our study. Mesonephric-like adenocarcinomas exhibit strikingly similar molecular aberrations to mesonephric adenocarcinomas, but also frequently harbor PIK3CA mutations, demonstrating biological overlap with carcinomas of both mesonephric and Mullerian (endometrioid) differentiation. Given the previously documented association with endometriosis(ovarian neoplasms) and the prominent endometrial involvement (uterine corpus neoplasms), we believe these are best regarded as of Mullerian origin and representing adenocarcinomas which differentiate along mesonephric lines; as such, we propose the term mesonephric-like Mullerian adenocarcinoma.

 

 

 

 

 

 

 

ILAR J. 2017 Dec 1;58(2):281-294.

Nonhuman Primates: A Vital Model for Basic and Applied Research on Female Reproduction, Prenatal Development, and Women’s Health.

Stouffer RL^1,2, Woodruff TK^3,4.

 

Abstract

The comparative biology of reproduction and development in mammalian species is remarkable. Hence, because of similarities in environmental and neuroendocrine control of the reproductive axis, the cyclic function of the ovary and reproductive tract, establishment and control of the maternal-fetal-placental unit during pregnancy, and reproductive aging from puberty through menopause, nonhuman primates (NHPs) are valuable models for research related to women’s reproductive health and its disorders. This chapter provides examples of research over the past 10+ years using Old World monkeys (notably macaque species), baboons, and to a lesser extent New World monkeys (especially marmosets) that contributed to our understanding of the etiology and therapies or prevention of: (1) ovarian disorders, e.g., polycystic ovary syndrome, mitochondrial DNA-based diseases from the oocyte; (2) uterine disorders, for example, endometriosis and uterine transplantation; and (3) pregnancy disorders, for example, preterm labor and delivery, environmental factors. Also, emerging opportunities such as viral (e.g., Zika) induced fetal defects and germline genomic editing to generate valuable primate models of human diseases (e.g., Huntington and muscular dystrophy) are addressed. Although the high costs, specialized resources, and ethical debate challenge the use of primates in biomedical research, their inclusion in fertility and infertility research is vital for continued improvements in women’s reproductive health.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Nov;218:123-128.

Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study.

Arya S¹, Kupesic-Plavsic S², Mulla ZD³, Dwivedi AK⁴, Crisp Z⁵, Jose J⁵, Noble LS⁶.

Abstract

OBJECTIVE:

To assess the effect of letrozole in combination with low dose gonadotropins for ovulation induction in anovulatory infertility from polycystic ovary syndrome (PCOS) and controlled ovarian stimulation for endometriosis, and unexplained infertility patients.

STUDY DESIGN:

Retrospective cohort study in a setting of private Reproductive Endocrinology and Infertility Clinic affiliated with the University. Three hundred couples (650 cycles) requiring OI/COS for PCOS (92 patients, 195 cycles), endometriosis (89 patients, 217 cycles), and unexplained infertility (119 patients, 238 cycles). Patients received 2.5mg or 5mg letrozole for 5days (D3-D7) and recombinant follicle-stimulating hormone on alternating D3-D7 and human menopausal gonadotropin-highly purified alternating D5-D10 until growth of ideally 2 mature follicles. Ovulation was triggered with 10,000 IU of HCG. Maximum number of cycles per patient was four.

RESULTS:

Main outcome measures were clinical pregnancy rates, multiple order pregnancy rates, miscarriage rates, number of follicles and endometrial thickness on the day of HCG administration. The cumulative incidence of pregnancy was estimated as 35% (95%CI: 29%-41%) overall and was highest in patients with PCOS (36.6%), followed by unexplained infertility (34.6%) and endometriosis (32.5%). The pregnancy rates per cycle in PCOS, endometriosis and unexplained infertility patients were 17%, 13.2% and 17.2% respectively, no statistically significant difference between the groups. There were three twin pregnancies in PCOS, and one in unexplained infertility group. Monofolliculogenesis was noted in 48% of patients.

CONCLUSION(S):

Letrozole-low dose gonadotropins combination appears to be effective across different causes of infertility for superovulation. The letrozole-low dose gonadotropin combination resulted in high rate of monofolliculogenesis, low occurrence of multiple gestations and no case of OHSS or cycle cancellation.

 

 

 

Emerg Radiol. 2018 Feb;25(1):107-110.

Uterine artery pseudoaneurysm in the setting of deep endometriosis: an uncommon cause of hemoperitoneum in pregnancy.

Feld Z¹, Rowen T², Callen A³, Goldstein R³, Poder L³.

 

Abstract

Uterine, ovarian, and placental pathologies are among the differential considerations for a pregnant woman presenting with abdominal and pelvic pain. Imaging plays a key role in the initial work-up of these patients. Sonography is often the first line test; however, evaluation of pelvic pathology can be limited in the gravid state, especially in mid- or late-term pregnancy. We present a case of a pregnant woman who came to the emergency room at 25 weeks with acute abdominal and pelvic pain. Both ultrasound and MR imaging findings revealed intraperitoneal hemorrhage, initially of unknown origin, as well as endometriomas and deep endometriosis. Only postpartum imaging confirmed a uterine artery pseudoaneurysm (PSA) presumably due to decidual reaction in deep endometriosis. We speculate the intraperitoneal hemorrhage was subsequently due to the PSA. This case demonstrates that if hemorrhage is not recognized promptly, it can lead to hemodynamic instability, as well as premature labor and delivery.

 

 

 

J Minim Invasive Gynecol. 2017 Oct 5

Comparison of Laparoscopic Discoid Resection and Segmental Resection for Colorectal Endometriosis Using a Propensity Score Matching Analysis.

Jayot A¹, Nyangoh Timoh K², Bendifallah S³, Ballester M⁴, Darai E⁴.

Abstract

STUDY OBJECTIVE:

Our primary endpoint was to compare the intra- and postoperative complications, whereas secondary endpoints were the occurrence of voiding dysfunction and evaluation of the quality or life of segmental and discoid resection in patients with colorectal endometriosis.

DESIGN:

Retrospective study (Canadian Task Force classification II-2).

SETTING:

Tenon University Hospital in Paris.

PATIENTS:

Thirty-one 31 patients who underwent a conservative surgery and 31 patients who underwent.

INTERVENTIONS:

The 2 groups were compared using propensity score matching (PSM) analysis, with a median follow-up of 247 days (8.2 months).

MEASUREMENTS AND MAIN RESULTS:

Discoid colorectal resection was associated with a shorter operating time (155 vs 180 minutes, p = .03) and hospital stay (7 vs 8 days, p = .002) than segmental colorectal resection; however, a similar intra- and postoperative complication rate was found. A higher rate of postoperative voiding dysfunction was observed in the segmental resection group (19% vs 45%, p = .03) as well as duration of voiding dysfunction requiring bladder self-catheterization longer than 30 days (0 vs 22%, p = .005).

CONCLUSION:

Our PSM analysis suggests the advantages of discoid resection because it results in a similar surgical complication rate to segmental resection but with advantages in operating time, hospital stay, and voiding dysfunction.

 

 

 

J Obstet Gynaecol Can. 2017 Oct 5.

Management of Endometriosis: Toward Value-Based, Cost-Effective, Affordable Care.

Vercellini P¹, Facchin F², Buggio L³, Barbara G⁴, Berlanda N⁴, Frattaruolo MP³, Somigliana E³.

 

Abstract

Endometriosis management seems to be influenced by outcome-independent biomedical, pharmacological, and technological developments. The propensity towards doing more affects several aspects of care, sometimes translating into proposals that are not based on sound epidemiological principles and robust evidence. Different stakeholders share the interest for doing more testing and using novel and costly drugs or devices in patients with endometriosis. Although some women may benefit from such an approach, the majority do not, and some may be harmed. Moreover, an uncontrolled increase in expenditures for endometriosis management without demonstrated and proportional health benefits would waste the finite resources of national health care services and would risk cost-related non-adherence. Cost-effectiveness analyses should be systematically pre-planned in future trials on endometriosis, and the concept of “value” of medical interventions should guide investigators and health care policymakers. Reducing low-value care, financial toxicity, and the burden of treatment is respectful not only of endometriosis patients, but also of the entire society. Whenever possible, long-term therapeutic strategies should be tailored to each woman’s needs, and high-value tests and treatments should be chosen based on her priorities and preferences. Moreover, listening to patients, understanding their concerns, avoiding disease labelling, explaining plainly what is known and what is unknown, and giving constant reassurance and encouragement may be exceedingly important for the successful management of endometriosis and may change the patient’s perception of her clinical condition. Physician empathy has no untoward effects, does not cause harms, and may determine whether a woman successfully copes or desperately struggles with her disease during reproductive life.

 

 

 

 

Mol Med Rep. 2017 Dec;16(6):8259-8264.

miRNA‑34a‑5p downregulation of VEGFA in endometrial stem cells contributes to the pathogenesis of endometriosis.

Ma Y¹, Huang YX¹, Chen YY¹.

 

Abstract

Endometrial-derived stem cells (EnSCs) serve an important role in the development of endometriosis via retrograde menstruation. Abnormal expression of miRNAs in EnSCs is involved in the etiology of endometriosis, however, the mechanisms remain unclear. The aim of the present study was to investigate the expression of miR‑34a‑5p and VEGFA in endometrial samples from patients with or without endometriosis, and then examine the underlying mechanism of microRNA‑34a‑5p regulation of VEGFA in EnSCs. Endometrial samples from patients with or without endometriosis were collected, and miR‑34a‑5p expression in the two groups was measured using RT‑PCR. Human endometrial‑derived stem cells (hEnSCs) were isolated from these endometrial samples, and hEnSCs were transfected with the miR‑34a‑5p mimics or control miRNAs. qPCR and western blotting were performed to assess the effects of miR‑34a‑5p on the expression of VEGFA in hEnSCs, and cell growth was assessed by an MTT assay. miR‑34a‑5p was significantly downregulated in patients with endometriosis when compared with that of those without endometriosis. VEGFA expression levels in hEnSCs with an overexpression of miR‑34a‑5p were significantly reduced when compared with those in the negative control (P<0.01). In addition, the upregulation of miR‑34a‑5p suppressed EnSCs proliferation by targeting the 3′ untranslated region of VEGFA. miR‑34a‑5p provides a novel avenue for the understanding of the development of endometriosis, and may facilitate the development of potential therapeutics against endometriosis.

 

 

 

J Med Imaging Radiat Oncol. 2017 Dec;61(6):767-773.

MRI findings in deep infiltrating endometriosis: A pictorial essay.

Thalluri AL¹, Knox S^1,2,3, Nguyen T^2,3.

 

Abstract

Endometriosis is an important gynaecological disorder which can impact significantly on an individual’s quality of life and has major implications on fertility. Deep infiltrating endometriosis is a severe form of endometriosis which can cause obliteration of anatomic compartments. Laparoscopy remains the gold standard for diagnosis of endometriosis, although is an invasive procedure that has the potential to be hindered by obliterative disease. Ultrasound is often employed as the first-line imaging modality when endometriosis is suspected, however, MRI is more accurate in assessment of complex disease. Pre-operative MRI is highly specific in the diagnosis of endometriosis and characterization of disease extent, and plays a key role in guiding surgical management. MRI findings in deep infiltrating endometriosis are described.

 

 

 

Clin Obstet Gynecol. 2017 Dec;60(4):711-727.

Endometriosis-associated Ovarian Cancers.

Anglesio MS¹, Yong PJ.

 

Abstract

Endometriosis-associated cancers include clear cell and endometrioid ovarian carcinoma. A history of endometriosis has long been considered to be a risk factor for later development of these malignancies; however, recent molecular genetic evidence has provided unequivocal evidence that these lesions are in fact the precursors for endometriosis-associated cancers. Herein, we will explore the relationship between endometriosis and ovarian carcinomas, similarities between the premalignant lesions and their cancerous counterparts, and the potential role of mutations and the ovarian microenvironment that may contribute to malignant transformation.

 

 

 

Am J Epidemiol. 2017 Jul 13.

A Prospective Study of Inflammatory Markers and Risk of Endometriosis.

Mu F, Harris HR, Rich-Edwards JW, Hankinson SE, Rimm EB, Spiegelman D, Missmer SA.

 

Abstract

A body of evidence suggests a role for inflammation in the pathogenesis of endometriosis. Numerous case-control studies have found that inflammatory markers were elevated in endometriosis cases compared to controls. However, results are not consistent and no prior prospective study exists. We conducted a case-control study study nested within the Nurses’ Health Study II examining the associations between plasma levels of interleukin-1 beta (IL-1ß), IL-6, soluble tumor necrosis factor α receptor-1 (sTNFR-1), sTNFR-2, and high-sensitivity C-reactive protein and laparoscopically-confirmed endometriosis risk. Between blood collection in 1996-1999 and 2007 we ascertained 350 incident endometriosis cases and 694 matched controls. Women in quintiles 2-4 of IL-1ß levels had an increased risk of endometriosis (2nd quintile, RR = 3.30 (95% CI = 1.06-10.3); 3rd quintile, RR = 3.36 (95% CI = 1.09-10.4); 4th quintile, RR = 4.64 (95% CI = 1.58-13.6); Ptrend = 0.62)), suggesting an association beginning at IL-1ß levels ≥0.47 pg/mL. A significant non-linear association with sTNFR-2 was observed, with an elevation in the risk of endometriosis when sTNFR-2 was > 3400 pg/ml. Plasma IL-6, sTNFR-1, and high-sensitivity C-reactive protein levels were not associated with endometriosis risk. Further research in larger studies with younger age at blood collection and longer time from blood to surgical diagnosis will be required to confirm these associations.

 

 

 

Reprod Sci. 2017 Jan 1:1933719117734319.

Composition of the Stroma in the Human Endometrium and Endometriosis.

Konrad L¹, Kortum J¹, Nabham R^1,2, Gronbach J¹, Dietze R¹, Oehmke F¹, Berkes E¹, Tinneberg HR¹.

 

Abstract

To analyze whether the endometrial and endometriotic microenvironment is involved in the pathogenesis of endometriosis, we characterized the stromal composition. We used CD90 for fibroblasts, α-smooth muscle actin for myofibroblasts as well as CD10 and CD140b for mesenchymal stromal cells. Quantification of eutopic endometrial stroma of cases without endometriosis showed a high percentage of stromal cells positive for CD140b (80.7%) and CD10 (67.4%), a moderate number of CD90-positive cells (57.9%), and very few α-smooth muscle actin-positive cells (8.5%). These values are highly similar to cases with endometriosis showing only minor changes: CD140b (76.7%), CD10 (63%), CD90 (53.9%), and α-smooth muscle actin (6.9%). There are no significant differences in the composition of CD140b- and CD10-positive stromal cells between the eutopic endometrial stroma and the 3 different endometriotic entities (ovarian, peritoneal, and deep infiltrating endometriosis), except for a significant difference between CD10-positive stromal cells in peritoneal lesions compared to ovarian lesions. However, the percentage of CD90-positive stromal cells was reduced in the 3 different endometriotic entities compared to the endometrium, especially significant in the ovarian lesions. In contrast, the percentage of α-smooth muscle actin-positive cells in the ovary was moderately increased. Taken together, the marker signature of eutopic endometrial and endometriotic stromal cells resembles mostly mesenchymal stromal cells. Our results show clearly that the proportion of the different stromal cell types in the endometrium with or without endometriosis does not differ significantly, thus suggesting that the stromal eutopic endometrial microenvironment does not contribute to the pathogenesis of endometriosis.

 

Ugeskr Laeger. 2017 Oct 9;179(41).

Umbilical endometriosis and tumours in umbilicus.

Juel J¹, Holst-Albrechtsen S, Erantaite D.

 

Abstract

Umbilical endometriosis is rare, representing only 0.5-1% of all cases of extragenital endometriosis. In infertile women, endometriosis may be as prevalent as 50%. Numerous differential diagnoses are present, hence the clinical diagnosis of umbilical tumours is intricate. In a 33-year-old woman, an umbilical tumour presented 12 months prior to referral. On referral, no cyclic bleeding was noticed, although intermittent bleeding and soreness of the element were present. Dysmenorrhoea, dyspareunia, intermittent pelvic pain, and three years of infertility were noted. A biopsy showed endometriosis.

 

 

 

J Minim Invasive Gynecol. 2017 Oct 6.

Discoid Resection of Rectosigmoid Endometriotic Nodules.

Stuparich MA¹, Lee TTM².

Abstract

STUDY OBJECTIVE:

To show various techniques to perform laparoscopic anterior discoid resection of rectosigmoid endometriotic nodules.

DESIGN:

A step-by-step explanation of the techniques using video with narration (educational video).

SETTING:

Segmental bowel resection and reanastomosis are treatment options for larger rectosigmoid endometriotic nodules. However, laparoscopic anterior discoid resection of rectosigmoid endometriotic nodules is feasible and potentially less morbid in the appropriate candidate. Detailed knowledge of the avascular planes of the pelvis, particularly the pararectal and rectovaginal spaces, is crucial when approaching these nodules, which may initially present within an obliterated posterior cul-de-sac. Resection begins with determination of the nodule size followed by enucleation of the nodule itself. A 2-layer closure with barbed suture is then performed using a rectal probe as a template. Our institution previously demonstrated that barbed suture is safe to use in bowel repair and did not result in major complications [1]. An air leak test assesses the integrity of the repair and may be completed with air insufflation or with a methylene blue or povidone-iodine enema. With larger nodules, a V-shaped closure may be necessary. The patients provided consent to use images and videos of the procedure. Institutional review board approval was not required for this procedure.

INTERVENTIONS:

Laparoscopic anterior discoid resection of a rectosigmoid endometriotic nodule.

CONCLUSION:

Laparoscopic anterior discoid resection avoids the need for segmental bowel resection and reanastomosis. Barbed suture is a safe option for 2-layer bowel closure [1].

 

 

 

Magn Reson Med Sci. 2017 Oct 6.

Differentiation of Seromucinous Borderline Tumor from Serous Borderline Tumor on MR Imaging.

Kurata Y¹, Kido A¹, Moribata Y¹, Kameyama K¹, Minamiguchi S², Konishi I^3,4, Togashi K¹.

Abstract

PURPOSE:

Seromucinous borderline tumor (SMBT) is a newly categorized ovarian tumor in the 2014 revised World Health Organization (WHO) classification. SMBT is similar to serous borderline tumor (SBT) on magnetic resonance imaging (MRI) reflecting their pathological findings. This study was conducted to demonstrate the usefulness of MRI findings and quantitative values for differentiating SMBT from SBT.

METHODS:

This retrospective study examined 23 lesions (20 patients) from SMBT and 26 lesions (22 patients) from SBT. The following quantitative values were evaluated using receiver-operating characteristics analysis: overall and solid portion sizes, intracystic fluid signal intensity (SI) ratio compared with skeletal muscle on T₁weighted image (T₁WI) and T₂weighted image (T₂WI), contrast enhancement (CE) ratio, and mean and minimum apparent diffusion coefficient values of the solid portion. Two radiologists evaluated the prevalence of MRI finding characteristics of SMBT and SBT. The SI of the intracystic fluid on T₁WI and T₂WI and the association with endometriosis were evaluated visually.

RESULTS:

The CE ratio was significantly higher in SBT (P = 0.007). It achieved the highest area under the curve (AUC) (0.739). The fluid SI ratio on T₁WI was higher in SMBT (P = 0.036, AUC = 0.676). Exophytic growth of the solid portion was observed only in SBT (P = 0.011). Intracystic fluid SI of SMBT was higher on T₁WI and lower on T₂WI in visual evaluation (P = 0.008 and 0.007, respectively). Findings suggesting endometriosis were observed more frequently in SMBT patients (P = 0.019).

CONCLUSION:

Higher CE ratio of the solid portion and exophytic growth were findings suggesting SBT. Higher intracystic fluid SI on T₁WI and lower SI on T₂WI suggested SMBT. MRI findings suggesting endometriosis favored the diagnosis of SMBT.

 

 

 

Angiogenesis. 2017 Oct 9.

Notch signaling controls sprouting angiogenesis of endometriotic lesions.

Körbel C¹, Gerstner MD¹, Menger MD¹, Laschke MW².

Abstract

Angiogenesis is essential for the engraftment and growth of endometriotic lesions. In this study, we analyzed whether this process is regulated by Notch signaling. Endometriotic lesions were induced by endometrial tissue transplantation into dorsal skinfold chambers of C57BL/6 mice, which were treated with the γ-secretase inhibitor DAPT or vehicle. Vascularization, morphology, and proliferation of the newly developing lesions were analyzed using intravital fluorescence microscopy, histology, and immunohistochemistry over 14 days. Inhibition of Notch signaling by DAPT significantly increased the number of angiogenic sprouts within the endometrial grafts during the first days after transplantation when compared to vehicle-treated controls. This was associated with an accelerated vascularization, as indicated by a higher functional microvessel density of DAPT-treated lesions on day 6. However, inhibition of Notch signaling did not affect the morphology and proliferating activity of the lesions, as previously described for tumors. Both DAPT- and vehicle-treated lesions finally consisted of cyst-like dilated glands, which were surrounded by a well-vascularized stroma and contained comparable numbers of proliferating cell nuclear antigen-positive cells. These findings demonstrate that sprouting angiogenesis in endometriotic lesions is controlled by Notch signaling. However, inhibition of Notch signaling does not have beneficial therapeutic effects on lesion development.

 

 

 

Int J Surg Case Rep. 2017;41:1-4.

Ovarian vein thrombosis after total laparoscopic hysterectomy with unilateral adnexectomy: A case report.

Al-Αchmar SN¹, Stavrou S², Protopapas A³, Drakakis P⁴, Siemou P⁵, Chatzipapas I⁶.

Abstract

INTRODUCTION:

Ovarian vein thrombosis is a rare but potentially serious complication after surgical and gynecologic procedures such as oophorectomy and hysterectomy. The association of this event with laparoscopic hysterectomy in particular, is very rare. Only two cases have been described so far.

PRESENTATION OF CASE:

We present a case of ovarian vein thrombosis after laparoscopic hysterectomy in a 40-year-old with deep endometriosis and multiple intramural uterine myomas. Laparoscopic hysterectomy, left oophorectomy, right salpingectomy, and suspension (ovariopexy) of the right ovary on the ipsilateral round ligament of the uterus were performed, using bipolar electrocautery as a hemostatic tool.

DISCUSSION:

The 7th postoperative day the patient presented to our hospital complaining of abdominal pain and fever. An abdominal CT scan demonstrated a filling defect and enlargement of the right ovarian vein, a finding compatible with ovarian vein thrombosis. She was treated with low molecular weight heparin (LMWH). On the 19th postoperative day, an MRI scan was performed and did not reveal any pathological findings of the right ovarian vein. The patient was discharged on LMWH for three months. Post treatment evaluation for thrombophilia was negative for pathological findings.

CONCLUSION:

Our case is a very rare condition. Only two ‘similar’ cases have been described in the literature so far. Bipolar electrocautery and ovariopexy on the ipsilateral round ligament during laparoscopic hysterectomy should be evaluated further as possible contributing mechanisms for the thrombus formation.

 

 

 

J Obstet Gynaecol. 2017 Oct 10:1-5.

Which factors are associated with the recurrence of endometrioma after cystectomy?

Küçükbaş M¹, Kurek Eken M², İlhan G³, Şenol T⁴, Herkiloğlu D¹, Kapudere B⁵.

 

Abstract

Endometrioma is the most common form of endometriosis and is a sign of wide-spread disease in symptomatic patients. Medical treatment options can be successful in endometrioma smaller than 1 cm, but ineffective for growing and symptomatic endometriomas. Conservative surgical interventions that preserve fertility, such as laparoscopic removal or destruction of endometriotic tissue or aspiration of cystic content are typically used to treat the condition. One of the most frustrating aspects of endometrioma treatment is disease recurrence. The underlying mechanisms explaining recurrence are uncertain. Several risk factors have been evaluated in order to predict recurrence after cystectomy. In looking at the results overall, our study can conclude that the presence of greater cyst dimension, higher CA-125 level, presence of preoperative symptoms of non-cyclic pelvic pain, dysmenorrhoea and adhesion extension may be associated with recurrent endometrioma. In clinical practice, identification of risk factors for recurrence helps clinicians to inform patients. Impact statement What is already known on this subject: Endometrioma is the most common form of endometriosis and is a sign of wide-spread disease in symptomatic patients. One of the most frustrating aspects of endometrioma treatment is disease recurrence. Several risk factors have been evaluated in order to predict recurrence after cystectomy. However, the risk factors have not been precisely defined. What the results of this study add: This study aimed to investigate the contribution of possible risk factors to the recurrence of endometrioma after laparoscopic surgery. In looking at the results overall, our study can conclude that the presence of greater cyst dimension, higher CA-125 level, adhesion extension, presence of preoperative symptoms of non-cyclic pelvic pain and dysmenorrhoea may be associated with recurrent endometrioma. What the implications of these findings are for clinical practice and/or further research: In clinical practice, identification of risk factors for recurrence helps clinicians to inform patients. Detection of preoperative risk factors would be helpful in counselling patients on their future prognosis. This may also increase treatment success by providing accurate preoperative treatment planning and by assisting the scheduling of postoperative follow-ups.

 

 

 

Reprod Sci. 2017 Jan 1:1933719117734320.

Aberrant Expression of lncRNA ( HOXA11-AS1) and Homeobox A ( HOXA9, HOXA10, HOXA11, and HOXA13) Genes in Infertile Women With Endometriosis.

Wang M^1,2, Hao C², Huang X², Bao H², Qu Q², Liu Z², Dai H², He S², Yan W².

 

Abstract

This study aimed to study the expression of homeobox (HOX)A11-AS1 ( HOXA11 antisense RNA) long noncoding RNA (lncRNA) and the expression of homeobox A ( HOXA9, HOXA10, HOXA11, and HOXA13) genes in the eutopic (EU) and ectopic (EC) endometria of women with peritoneal endometriosis. A total of 30 women undergoing laparoscopic surgery for peritoneal endometriosis and 15 infertile women without endometriosis were enrolled in this study. Peritoneal EC tissue samples were obtained through surgery. The EU tissues were obtained by curettage. The EC and EU lncRNA and messenger RNA (mRNA) expression levels were measured using real-time reverse transcriptase-polymerase chain reaction. The HOXA11-AS1 lncRNA and HOXA9, HOXA10, HOXA11, and HOXA13 mRNA were expressed at significantly lower levels in the EU than in the EC, that is, in women with peritoneal endometriosis ( P < .05). The expression levels of HOXA10 and HOXA11 in the EU were significantly lower in women with peritoneal endometriosis compared to the control group participants ( P < .05), whereas the levels of lncRNA ( HOXA11-AS1), HOXA9, and HOXA13 did not differ significantly between the 2 patient groups ( P > .05). In conclusion, the study findings suggest that HOXA11-AS1 lncRNA may play a role in the development of peritoneal endometriosis, but HOXA11-AS1 may not influence endometrial receptivity in endometriosis-associated infertility.

 

 

 

Reprod Sci. 2017 Nov;24(11):1532-1537.

High Expression of High-Mobility Group Box 1 in Menstrual Blood: Implications for Endometriosis.

Shimizu K^1,2, Kamada Y¹, Sakamoto A^1,2, Matsuda M^1,2, Nakatsuka M^1,3, Hiramatsu Y^1,2.

 

Abstract

Endometriosis is a benign gynecologic disease characterized by the presence of ectopic endometrium and associated with inflammation and immune abnormalities. However, the molecular basis for endometriosisis not well understood. To address this issue, the present study examined the expression of high-mobility group box (HMGB) 1 in menstrual blood to investigate its role in the ectopic growth of human endometriotic stromal cells (ESCs). A total of 139 patients were enrolled in this study; 84 had endometriosis and 55 were nonendometriotic gynecological patients (control). The HMGB1 levels in various fluids were measured by enzyme-linked immunosorbent assay. Expression of receptor for advanced glycation end products (RAGE) in eutopic and ectopic endometrium was assessed by immunohistochemistry, and RAGE and vascular endothelial growth factor ( VEGF) messenger RNA expression in HMGB1- and lipopolysaccharide (LPS)-treated ESCs was evaluated by real-time polymerase chain reaction. The HMGB1 concentration was higher in menstrual blood than in serum or peritoneal fluid ( P < .001 for both). RAGE was expressed in both normal and ectopic endometrium. Administration of 1000 ng/mL HMGB1 or coadministration of 100 ng/mL HMGB1 and 100 ng/mL LPS induced VEGF production in ESCs relative to the control ( P < .05). These results suggest that menstrual fluid has naturally high levels of HMGB1 and may promote endometriosis following retrograde menstruation when complexed with other factors such as LPS by inducing inflammation and angiogenesis.

 

 

Reprod Fertil Dev. 2017 Oct 11.

Expression of vascular endothelial growth factor A isoforms is dysregulated in women with endometriosis.

Danastas K, Miller EJ, Hey-Cunningham AJ, Murphy CR, Lindsay LA.

 

Abstract

Angiogenesis is a critical step in the development of ectopic lesions during endometriosis. Although total vascular endothelial growth factor (VEGF) A is elevated in the peritoneal fluid of women with endometriosis, there are contradictory reports on how levels of total endometrial VEGFA are altered in this disease. Furthermore, limited research is available on different VEGFA isoforms in women with endometriosis. Thus, the aim of the present study was to analyse levels of various VEGFA isoforms in women with and without endometriosis at different stages of the menstrual cycle. Quantitative polymerase chain reaction analysis showed that total VEGFA was highest during menstruation in endometriosiscompared with controls (P=0.0373). VEGF121 and VEGF189 were similarly highest during menstruation in endometriosis compared with controls (P=0.0165 and 0.0154 respectively). The present study is also the first to identify the natural expression of VEGF111 in human tissue, which is also highest during menstruation in endometriosis (P=0.0464). This discovery of the natural production of VEGF111 in human endometrium, as well as the upregulation of VEGFA isoforms during menstruation in endometriosis, may shed further light on the development and progression of the disease, and improve our understanding of the regulation of endometrial angiogenesis.

 

 

 

Arch Gynecol Obstet. 2018 Jan;297(1):117-123.

Knockdown of E-cadherin expression of endometrial epithelial cells may activate Wnt/β-catenin pathway in vitro.

Zhu X¹, Li Y², Zhou R², Wang N², Kang S³.

Abstract

PURPOSE:

E-cadherin, a transmembrane glycoprotein mediating Ca²⁺-independent homotypic cell-cell adhesion in epithelial cell, plays an essential role in metastasis. It has been postulated that E-cadherin downregulation is a crucial mechanism in the pathogenesis of endometriosis. To evaluate the effect on the cell behavior after knockdown of E-cadherin gene (CDH1) in cultured human endometrial epithelial cells (EECs) isolated from normal endometrium.

METHODS:

EECs were isolated from the endometrial tissues of fertile woman who underwent total hysterectomy due to cervical intraepithelial neoplasia III. CDH1 expression was knocked down by small hairpin RNA. The EECs transfected with empty vector served as control. Transwell assay was used to test EECs migration or invasion. qRT-PCR and western blot were used to detect mRNA and protein levels.

RESULTS:

The results showed that knockdown of E-cadherin expression can increase cell migration and invasion, and up-regulate mRNA and protein levels of β-catenin, cyclinD1, and c-myc.

CONCLUSIONS:

Down-regulation of E-cadherin expression may activate the Wnt/β-catenin pathway in endometrial cells, which may together participate in the occurrence of endometriosis.

 

 

 

Ceska Gynekol. 2017 Fall;82(5):411-418.

Endometriosis and quality of life.

Koliba P, Kužel D, Fanta M.

Abstract

OBJECTIVE:

This article aims to provide a comprehensive overview of the possibilities of evaluating the impact of symptoms of endometriosis on quality of life of affected women and to overview the effect of treatment modalities in improving of the quality of their life.

DESIGN:

Review article.

SETTING:

Department of Obstetrics and Gynecology, First Faculty of Medicine, Charles University and General University Hospital in Prague.

METHODS:

Review of results of published studies evaluating quality of life in patients with endometriosis.

CONCLUSION:

Symptoms of endometriosis decrease the quality of life of affected women, which has significant impact on society. Since the extent of endometriosis does not correlate with subjective complaints, it is suitable to evaluate the quality of life of patients in addition to assessment of the extent and classification of the disease (according to internationally accepted classification). The quality of life could be measured and compared by structured interviews or by validated questionnaires. Pharmacological as well as surgical treatment significantly improve quality of life of patients with endometriosis. Routine use of validated questionnaires of quality of life in patients with endometriosismight improve the assessment of severity of the disease and evaluation of effectiveness of the treatment in the future.

 

 

 

Indian J Urol. 2017 Oct-Dec;33(4):276-282.

Ureteral endometriosis: A systematic literature review.

Palla VV¹, Karaolanis G², Katafigiotis I³, Anastasiou I³.

Abstract

INTRODUCTION:

Ureteral endometriosis is a rare disease affecting women of childbearing age which presents with nonspecific symptoms and it may result in severe morbidity. The aim of this study was to review evidence about incidence, pathogenesis, clinical presentation, diagnosis, and management of ureteral endometriosis.

MATERIALS AND METHODS:

PubMed Central database was searched to identify studies reporting cases of ureteral endometriosis. “Ureter” or “Ureteral” and “Endometriosis” were used as key words. Database was searched for articles published since 1996, in English without restrictions regarding the study design.

RESULTS:

From 420 studies obtained through database search, 104 articles were finally included in this review, including a total of 1384 patients with ureteral endometriosis. Data regarding age, location, pathological findings, and interventions were extracted. Mean patients’ age was 38.6 years, whereas the therapeutic arsenal included hormonal, endoscopic, and/or surgical treatment.

CONCLUSIONS:

Ureteral endometriosis represents a diagnostic and therapeutic challenge for the clinicians and high clinical suspicion is needed to identify it.

 

 

 

 

 

Pak J Biol Sci. 2017;20(6):289-297.

Effect of Antioxidants on Testicular iNOS and eNOS after High-Fat Diet in Rat.

Sohrabi M¹, Hosseini M¹, Inan S², Alizadeh Z³, Vahabian M¹, Vahidinia AA⁴, Lahoutian H¹.

Author information

Abstract

BACKGROUND AND OBJECTIVE:

Spermatogenesis is a process by which germ cells produce spermatozoa and can be disturbed at every level. Nitric Oxide Synthases (NOS), implicate in interactions with Oxidative Stress (OS) which is one of the main factors in the etiology of male infertility. The High Fat Diet (HFD) is a major factor of obesity which in turn is important for enhancing OS. Antioxidants and garlic could attenuate or reverse effects of HFD. The aim of the study was to investigate the effects of dietary antioxidants and garlic on testicular inducible NOS (iNOS) and endothelial NOS (eNOS) in Wistar albino rats fed on HFD.

MATERIALS AND METHODS:

Groups (each n = 8) were: SD (100% access to standard diet), F-HFD, (100% access to HFD) and R-HFD (70% access to HFD), F-HFD +antioxidants, F-HFD+garlic and R-HFD+antioxidants. The HFD consisted of a 60% fatty diet in 3 forms: Without antioxidants, with antioxidants and with garlic. The testicular iNOS and eNOS were studied by immunohistochemical (IHC) method. Also used ANOVA, repeated measures ANOVA, t-tests and Tukey’s test (where necessary) to analyze the data (p<0.05).

RESULTS:

The iNOS increased in the F-HFD and R-HFD+antioxidants groups. The eNOS increased in R-HFD,F-HFD and F-HFD+garlic groups. The H-E evaluation in R-HFD group showed a decrease in spermatogenesis score count and seminiferous tubules diameters (μm) in comparison with the SD and F-HFD groups. R-HFD+antioxidants group had lower score than F-HFD+antioxidants and F-HFD+garlic groups.

CONCLUSION:

Restricted fat diet consumption causes increase in weight and impairs spermatogenesis. Results of this study reveal that adding the antioxidants can’t improve histological changes of testis. The iNOS expression in seminiferous tubules in restricted fat diet along with antioxidants, suggest a potential role of iNOS in spermatogenesis and male infertility.

 

 

 

 

 

J Laparoendosc Adv Surg Tech A. 2017 Oct 12.

Depth of Intestinal Wall Infiltration and Clinical Presentation of Deep Infiltrating Endometriosis: Evaluation of 553 Consecutive Cases.

Rossini R¹, Lisi G², Pesci A³, Ceccaroni M⁴, Zamboni G³, Gentile I¹, Rettore L¹, Ruffo G¹.

Abstract

INTRODUCTION:

Intestinal involvement in endometriosis was first described by Sampson in 1922. The reported incidence ranges between 3% and 37% in patients diagnosed with endometriosis. In literature, there are few studies that correlate the severity of endometriosis (in terms of intestinal infiltration) and its clinical presentation. The aim of this study was to review the correlation between the severity of symptoms, the depth of intestinal wall infiltration, and lymph node involvement in our tertiary referral center.

MATERIALS AND METHODS:

We retrospectively analyzed 553 patients who had undergone intestinal resection for deep infiltrating endometriosis at our institution (Sacro Cuore Negrar Hospital) between 2004 and 2009. Based on intestinal wall infiltration, we divided patients into three groups (Group A: intestinal infiltration that reaches the muscle layer, Group B: infiltration to the submucosa, and Group C: endometriosis reaches the mucosa). Symptoms, intestinal stenosis, and positive lymph nodes were compared in the three groups with the chi-square test.

RESULTS:

No statistical correlation was found between symptoms and the intestinal wall infiltrations. The three groups were also compared on the basis of positive visceral lymph nodes and we did find a statistical difference (P = .05) in the lymph node count in the two main groups.

CONCLUSION:

There seems to be no statistically significant difference in symptoms between patients with different degrees of infiltration. Although visceral lymph node involvement has been occasionally described in literature, we found that it is related to submucosal infiltration.

 

 

 

Ultrasound Obstet Gynecol. 2017 Oct 11.

Pelvic floor muscle assessment at 3-and 4-dimensional transperineal ultrasound in women with endometriosis, with or without retroperitoneal infiltration: a step towards complete functional assessment.

Mabrouk M^1,2, Raimondo D¹, Del Forno S¹, Baruffini F¹, Arena A¹, Benfenati A¹, Youssef A³, Martelli V¹, Seracchioli R¹.

Abstract

OBJECTIVES:

Previous studies, comparing women with deep infiltrating endometriosis (DIE) and healthy controls, underlined an association between pelvic floor muscle (PFM) hypertonic dysfunction and deep lesions. The aim of the study is to compare the morphometry of pelvic floor muscle (PFM) in women affected by ovarian endometriosis with or without DIE, to assess the impact of retroperitoneal infiltration by the disease on PFM function.

METHODS:

A prospective study was conducted between March 2015 to December 2016 on symptomatic women with clinical and sonographic diagnosis of ovarian endometriosis with or without DIE, submitted to laparoscopic surgery. We excluded patients with current or previous pregnancies, previous surgery for deep endometriosis, other causes of chronic pelvic pain, congenital or acquired abnormalities of pelvic floor anatomy. Transperineal, three-dimensional (3D) and four-dimensional (4D) ultrasound for evaluation of PFM morphometry was performed to assess levator hiatus area (LHA) and diameters at rest, during PFM contraction and during Valsalva manoeuvre. All volumes were offline analyzed by an investigator blinded to the clinical data.

RESULTS:

One-hundred fourteen patients were enrolled in the study: 75 with ovarian endometriosisassociated with DIE (DIE group) and 39 with isolated ovarian endometriosis (OVA group). Diagnosis of endometriosis was confirmed by histological examination in all patients. Compared to women in OVA group, women in DIE group showed a smaller LHA at rest, during contraction and during Valsalva manoeuvre (p = 0.03, p = 0.03, p = 0.02, respectively) and a smaller change in LHA narrowing during PFM contraction (p = 0.04).

CONCLUSIONS:

Women affected by DIE, compared to women with isolated ovarian endometriosis, presented more severe PFM dysfunctions. Because PFM dysfunctions in patients with DIE could be an important cause of pain symptoms and pelvic organ’s dysfunctions, transperineal ultrasound could allow a more complete functional assessment and a tailored therapy.

 

 

 

 

Int J Surg Case Rep. 2017;41:17-19.

A case report of endometriosis presenting as an acute small bowel obstruction.

Chan DL¹, Chua D², Ravindran P², Perez Cerdeira M², Mor I².

Abstract

INTRODUCTION:

Endometriosis is a common and benign condition that causes significant morbidity to women of childbearing age. It uncommonly affects the gastrointestinal tract and rarely manifests as an acute small bowel obstruction.

PRESENTATION OF CASE:

A 46-year old female presented to the emergency department with signs and symptoms consistent with an acute small bowel obstruction. She had a paucity of background surgical history, having only had a laparoscopic cholecystectomy. Her CT demonstrated small bowel obstruction with a transition point in the distal ileum. Given the site of obstruction was remote from previous surgery, a high index of suspicion was maintained and early laparoscopy performed the same day. Operative findings were consistent with an endometrial stricture of the distal ileum and a formal resection was performed.

DISCUSSION:

Endometriosis that affects the gastrointestinal tract often presents with non-specific symptoms. This is a rare case of an acute small bowel obstruction as the index symptom of endometriosisin a peri-menopausal patient. This is the first case in the literature to describe same day laparoscopy and small bowel resection of such a case and a prolonged preoperative period and misdiagnoses previously described were avoided due to clinical suspicion.

CONCLUSION:

Endometriosis as a differential should be considered with a high index of suspicion in pre-menopausal women, particularly in patients with negligible previous surgical history. There should be a low threshold for early laparoscopy and resection of affected bowel in these patients.

 

 

 

Int J Womens Health. 2017 Sep 27;9:711-716.

Possibility of using superoxide dismutase and glutathione peroxidase as endometriosis biomarkers.

Ekarattanawong S¹, Tanprasertkul C², Somprasit C², Chamod P¹, Tiengtip R¹, Bhamarapravatana K¹, Suwannarurk K².

Abstract

OBJECTIVE:

To study the possibility of using superoxide dismutase (SOD) and glutathione peroxidase (GPx) as combined preoperative biomarkers for endometriosis.

PARTICIPANTS AND METHODS:

Female patients aged between 18 and 45 years old who came to the Gynecology outpatient clinic, Thammasat University Hospital, during September 2013-2016 with the complaint of gynecologic symptoms suspected of endometriosis, and who were positively diagnosed with endometriosis, were included in this study. All patients underwent conservative laparoscopic ovarian cystectomy with histopathological report. The control group consisted of healthy females of reproductive age who came to the outpatient clinic. The plasma SOD and GPx were measured from blood samples with commercial kits. A receiver operating characteristic curve was generated for plasma activity of SOD, GPx, and combined tests. The cutoff values were selected at the most appropriate sensitivity and specificity.

RESULT:

All 36 cases were included in this study. Mean ages of patients in the patient and control groups were 33.1 and 28.6 years old, respectively. SOD and GPx activities of disease and control group were 6.15 and 8.11, 463.9 and 472.34 nmole/min/mL unit, respectively. The sensitivity and 1-specificity of the combined test were calculated at 0.78, with sensitivity, specificity, accuracy, positive predictive value, and negative predictive value being 68.75, 80.77, 76.50, 69.23, and 80.33, respectively.

CONCLUSION:

A combination testing of SOD and GPx can possibly be used as preoperative biomarker for endometriosis.

 

 

 

J Obstet Gynaecol Res. 2017 Dec;43(12):1870-1879.

Diagnostic performance of human epididymis protein 4 compared to a combination of biophysical and biochemical markers to differentiate ovarian endometriosis from epithelial ovarian cancer in premenopausal women.

Nikolova T¹, Zivadinovic R², Evtimovska N³, Klisarovska V⁴, Stanojevic M², Georgievska J⁵, Nikolova N¹.

Abstract

AIM:

This study is a comparison of human epididymis protein 4 (HE4) with cancer antigen 125 (CA125), using the Risk of Ovarian Malignancy Algorithm (ROMA), Copenhagen Index (CPH-I), Risk of Malignancy Index (RMI) and Morphology Index (MI) to differentiate ovarian endometriosis from epithelial ovarian cancer (EOC) in premenopausal women.

METHODS:

The study was performed at the University Clinic of Obstetrics and Gynecology in Skopje. One hundred and sixty-four premenopausal patients were divided into three study groups, including ovarian endometriosis (37), other benign pelvic masses (57) and EOCs (11), and a control group (59). After ultrasonography, all subjects underwent blood sampling. Surgery and histological verification was performed. Pelvic masses were classified based on histological findings. Mann-Whitney, receiver operating characteristic-area under the curve (AUC), sensitivity, specificity and Kruskal-Wallis tests were used for statistical analysis. The level of significance α was set at 5%.

RESULTS:

For each of the tested markers, sensitivity, specificity and accuracy to distinguish ovarian endometriosis from EOC were as follows: HE4 (81.82%, 100%, 95.83%); CA125 (81.82%, 48.65%, 56.25%); ROMA (90.91%, 83.78%, 85.42%); CPH-I (81.82%, 97.30%, 93.75%); RMI (90.91%, 35.14%, 47.92%); and MI (100%, 75.68%, 81.25%), respectively. The AUC for ovarian endometriosis compared to EOC for tested markers was as follows: HE4 (AUC = 0.934), CA125 (AUC = 0.821), ROMA (AUC = 0.929), CPH-I (AUC = 0.924) and RMI (AUC = 0.880), respectively.

CONCLUSION:

HE4 and CPH-I perform best to discriminate ovarian endometriosis from EOC in premenopausal women. MI has maximal sensitivity to detect EOC.

 

 

 

J Psychosom Obstet Gynaecol. 2017 Oct 13:1-6.

Mental health, pain symptoms and systemic comorbidities in women with endometriosis: a cross-sectional study.

Vannuccini S¹, Lazzeri L¹, Orlandini C¹, Morgante G¹, Bifulco G², Fagiolini A³, Petraglia F⁴.

Abstract

INTRODUCTION:

Endometriosis is a gynecological disease with a severe impact on quality of life. The aim of this study is to assess mental health status in a group of women with endometriosis, investigating their clinical history, pain symptoms and systemic comorbidities.

METHODS:

An observational cross-sectional study was performed on a group of Italian Caucasian women with endometriosis (n = 134). All patients filled the ‘Patient Health Questionnaire’ (PHQ), a self-administered screening tool for mental health disorders. The characteristics of endometriosis, pain symptoms and their severity, the presence and types of comorbid systemic disorders were added into the same survey.

RESULTS:

According to PHQ algorithms, 59% of patients were affected by at least one psychiatric disorder, with a significant correlation with pain symptoms (p = 0.0026). Patients with severe pain showed a higher incidence of multiple psychiatric disorders (p = 0.026) and somatoform disorder than those with mild pain (p = 0.0009). There was no correlation between the presence of psychiatric disorders and age, BMI, parity, infertility, need for surgery, number of intervention, localization of endometriotic lesions and systemic comorbidities.

DISCUSSION:

Women with endometriosis showed a high frequency of PHQ results positive for psychiatric disorders, with a significant association with pain severity.

 

 

 

Acta Obstet Gynecol Scand. 2018 Jan;97(1):59-67.

Trends in the incidence rate, type and treatment of surgically verified endometriosis – a nationwide cohort study.

Saavalainen L¹, Tikka T¹, But A², Gissler M^3,4, Haukka J², Tiitinen A¹, Härkki P¹, Heikinheimo O¹.

Abstract

INTRODUCTION:

To study the trends in incidence rate, type and surgical treatment, and patient characteristics of surgically verified endometriosis during 1987-2012.

MATERIAL AND METHODS:

This is a register-based cohort study. We identified women receiving their first diagnosis of endometriosis in surgery from the Finnish Hospital Discharge Register (FHDR). Quality of the FHDR records was assessed bidirectionally. The age-standardized incidence rates of the first surgically verified endometriosis was assessed by calendar year.

RESULTS:

The cohort comprises 49 956 women. The quality assessment suggested the FHDR data to be of good quality. The most common diagnosis, ovarian endometriosis (46%), was associated with highest median age 38.5 years (interquartile range 31.0-44.8) and the second most common diagnosis, peritoneal endometriosis (40%), with median age 34.9 years (28.6-41.7). Between 1987 and 2012, a decrease was observed in the median age, from 38.8 (32.3-43.6) to 34.0 (28.9-41.0) years, and in the age-standardized incidence rate from 116 [95% confidence interval (CI) 112-121] to 45 (42-48) per 100 000 women. The proportion of hysterectomy as a first surgical treatment decreased from 38 to 19%, whereas that of laparoscopy increased from 42 to 73% when comparing 1987-1995 with 1996-2012.

CONCLUSIONS:

This nationwide cohort of surgically verified endometriosis showed a decrease in the incidence rate and in the patient age at the time of first diagnosis, even though the proportion of laparoscopy has increased. The number of hysterectomies has decreased. These changes are likely to reflect the evolving diagnostics, increasing awareness of endometriosis, and effective use of medical treatment before surgery.

 

 

 

J Pediatr Adolesc Gynecol. 2017 Oct 10.

Obstructive Müllerian Anomalies in Menstruating Adolescent Girls: A Report of 22 Cases.

Kapczuk K¹, Friebe Z², Iwaniec K², Kędzia W².

Abstract

STUDY OBJECTIVE:

To assess the clinical course of obstructive Müllerian anomalies found in girls after menarche.

DESIGN:

A retrospective case series of adolescents who, between 2009 and 2016, were treated for vaginal or uterine obstructive malformations diagnosed after menarche.

SETTING:

Division of Gynecology, Poznań University of Medical Sciences, Poznań, Poland.

PARTICIPANTS AND INTERVENTIONS:

Twenty-two patients who, at the age range between 11.4 and 18.2 (median, 13.1) years, between 2 and 74 (median 7.5) months after menarche, underwent surgical repair of obstructive genital anomaly.

MAIN OUTCOME MEASURES:

Müllerian defect type, presentation, radiologic findings, pre- and postoperative course.

RESULTS:

Eighteen patients (18 of 22; 81.8%) were diagnosed with obstructed hemivagina ipsilateral renal anomaly syndrome. One patient (1 of 22; 4.5%) was diagnosed with uterus didelphys and unilateral cervical atresia. Three patients (3 of 22; 13.6%) had unicornuate uterus with a cavitated, noncommunicating rudimentary horn. The right side was affected in 13 patients (13 of 22; 59.1%), and the left side in 9 patients (9 of 22; 40.9%; P > .05). All but 1 patient had renal agenesis on the side of obstruction. Before repair of the obstructive genital anomaly, 4 patients underwent unnecessary surgeries for misdiagnosed ovarian cysts. Serious complications (pelvic inflammatory disease, vesicovaginal fistula) occurred in 2 patients with microperforated pyocolpos. Pelvic endometriosis was found in 4 of our patients.

CONCLUSION:

Our case series suggests that obstructed hemivagina ipsilateral renal anomaly syndrome is the most common obstructive Müllerian anomaly diagnosed in adolescents after menarche. The differential diagnosis for unilateral kidney agenesis accompanied by dysmenorrhea in adolescent girls should include obstructive genital tract anomaly. Accurate diagnosis of an obstructive genital anomaly early after menarche might help prevent unnecessary surgeries and infection-related complications. Meanwhile, prompt surgical correction of an obstructive genital tract anomaly results in relief of symptoms and might reduce the risk of endometriosis.

 

 

 

J Minim Invasive Gynecol. 2017 Oct 10.

Multidisciplinary Resection of Deeply Infiltrative Endometriosis.

Moawad GN¹, Tyan P², Abi Khalil ED², Samuel D³, Obias V⁴.

Abstract

STUDY OBJECTIVE:

To describe a multidisciplinary approach for the resection of deeply infiltrative endometriosis using the robotic platform.

DESIGN:

A technical video showing a step-by-step approach for the resection of deeply infiltrative endometriosis (Canadian Task Force classification level III). Institutional review board approval was not required for this study.

SETTING:

There is considerable involvement of the bowel and bladder with deeply infiltrative endometriosis [1-3]. The need for operative procedures involving multiple organs while performing a complete resection is common. The benefits of minimally invasive surgery for a gynecologic pathology have been documented in numerous studies. Patients had fewer medical and surgical complications postoperatively, better cosmesis, and better quality of life [4-6]. We believe that deeply infiltrative endometriosis does not preclude patients from having a minimally invasive resection procedure. In this video, we describe how the robotic platform was used for a seamless transition between surgical specialties including gynecology, colorectal, and urology to ensure complete resection of endometriosislesions involving multiple organs.

PATIENT:

A 47-year-old woman with a 4-year history of severe pelvic pain, dysuria, dyspareunia, dyschezia, and dysmenorrhea failing multiple medical therapies presented to our clinic to discuss surgical options. After thorough counseling, the decision was made to proceed with definitive surgical management. Postoperatively, the patient was admitted for 2 days of postoperative inpatient care. After meeting all immediate postoperative milestones, she was discharged with an indwelling Foley catheter and instructed to follow up in the clinic with all 3 surgical specialties. At the 1-week interval, she was seen by the urology team; her indwelling catheter was removed after a cystoscopy was performed documenting adequate healing. Two weeks postoperatively, the patient was seen by the gynecology and colorectal teams and was noted to be healing adequately from the procedure. Her six-week visit was also unremarkable. She continued to follow up with the gynecology team for her yearly well-woman examinations and has been symptom free for 2 years after the surgery. She takes norethindrone daily to minimize recurrence.

INTERVENTIONS:

Preoperative pelvic magnetic resonance imaging (MRI) showed bladder endometriosisand extensive rectovaginal endometriosis. We describe the multidisciplinary approach used for surgery and the procedures performed by each specialty. The urology team performed a cystoscopy preoperatively to assess for full-thickness erosions and the location of those lesions in that event. The urology team also reviewed the magnetic resonance images with the radiology team, and the endometriosis lesions were suspected to be close to the bladder trigone, keeping in mind that this finding could be overestimated given that the bladder was deflated at the time the imaging was obtained. Accordingly, at the time of surgery, the decision was made to proceed with cystoscopy and the placement of ureteral stents as a prophylactic measure. An intentional cystotomy and resection of the bladder section involved with endometriosis were performed followed by watertight closure. The trigone area of the bladder was not involved, and ureteral reimplantation was not needed in this case. The gynecology team operated second and performed an extensive dissection of the retroperitoneal space with the development of the pararectal and paravesical spaces. They also ligated the uterine artery at its origin followed by dissection of the uterovesical space, effectively reflecting the bladder off of the lower uterine segment. At this point, they proceeded with a total hysterectomy, and the specimen was removed from the pelvis through the vaginal cuff. Preoperatively, the colorectal surgeon ordered a colonoscopy to determine if full-thickness erosions were present and reviewed the magnetic resonance images with the radiology team. Based on the MRI and colonoscopy, all patients are counseled and consented for the possibility of a low anterior resection and loop ileostomy to protect the anastomosis. Based on the understanding that colorectal and gynecologic surgeries have a different approach when dissecting the pararectal space at our institution, a discussion between the 2 teams is initiated at the multidisciplinary session for surgery planning. In the case we present, the colorectal surgeon opted for the removal of the uterus before his dissection was initiated given that he dissects this space presacrally and not retroperitoneally like the gynecology counterpart. He would also benefit from the extra space for dissection with the uterus out of the pelvis. The colorectal part of the case was initiated by mobilization of the rectum and dissecting the obliterated rectovaginal space. The presacral space was then opened followed by mobilization of the rectosigmoid from its attachment. The case was concluded with full transection and reanastomosis of the rectum section involved with endometriosis. The specimen was also removed from the pelvis through the vaginal cuff.

MEASUREMENTS AND MAIN RESULTS:

Complete resection of deeply infiltrative endometriosis spanning beyond the scope of 1 surgical specialty. No immediate intraoperative, perioperative, or long-term complications from surgery. Complete resolution of endometriosis symptoms.

CONCLUSION:

We encourage collaborative care for planning and performing comprehensive and safe resection of deeply infiltrative endometriosis.

 

 

 

BJOG. 2017 Oct 14.

Epidemiology of infertility in China: a population-based study.

Zhou Z^1,2,3, Zheng D^1,2,3, Wu H^1,2,3, Li R^1,2,3, Xu S⁴, Kang Y⁵, Cao Y⁶, Chen X⁷, Zhu Y⁸, Xu S⁹, Chen ZJ¹⁰, Mol BW^11,12, Qiao J^1,2,3,13,14.

Abstract

OBJECTIVE:

To assess the current prevalence of and risk factors for infertility among couples of reproductive age in China.

DESIGN:

Population-based cross-sectional study.

SETTING:

We approached 25 270 couples in eight provinces/municipalities, of whom 18 571 (response rate 74%) were interviewed.

POPULATION:

Couples living together and married for more than 1 year, of whom the female spouse was 20-49 years old.

METHODS:

Women were approached via telephone and face-to-face conversation to complete the standardised and structured questionnaire by trained interviewers.

MAIN OUTCOME MEASURES:

Prevalence of and risk factors for infertility.

RESULTS:

Among women ‘at risk’ of pregnancy, the prevalence of infertility was 15.5% (2680/17 275). Among 10 742 women attempting to become pregnant, the prevalence of infertility was 25.0% (2680/10 742), which increased with age in the second population. Among women who failed to achieve pregnancy in the last 12 months, 3470 finished our questionnaire about fertility care, and 55.2% (1915/3470) of them had sought medical help. Sociodemographic risk factors for infertility included lower educational level [adjusted odds ratio (aOR) 3.4, 95% CI 2.0-5.5] and employment (aOR 2.3, 95% CI 1.9-2.9). Clinical risk factors were irregular menstrual cycle (aOR 1.8, 95% CI 1.2-2.5), light menstrual blood volume (aOR 1.6, 95% CI 1.2-2.0), history of cervicitis (aOR 1.5, 95% CI 1.2-2.0) and endometriosis (aOR 3.1, 95% CI 1.1-9.3), previous stillbirth (aOR 2.1, 95% CI 1.3-3.3) and miscarriage (aOR 2.7, 95% CI 2.1-3.5). In addition, history of operation was a significant risk factor of infertility.

CONCLUSIONS:

Among couples of reproductive age in China, the prevalence of infertility was 25%, and almost half of the couples experiencing infertility had not sought medical help.

TWEETABLE ABSTRACT:

In China, 25% of couples actively attempting to become pregnant suffered infertility.

 

 

 

Am J Obstet Gynecol. 2018 Jan;218(1):114.e1-114.e12.

Chronic pelvic pain in an interdisciplinary setting: 1-year prospective cohort.

Allaire C¹, Williams C², Bodmer-Roy S², Zhu S³, Arion K³, Ambacher K³, Wu J³, Yosef A⁴, Wong F⁵, Noga H⁵, Britnell S³, Yager H³, Bedaiwy MA¹, Albert AY⁶, Lisonkova S⁷, Yong PJ⁸.

Abstract

BACKGROUND:

Chronic pelvic pain affects ∼15% of women, and presents a challenging problem for gynecologists due to its complex etiology involving multiple comorbidities. Thus, an interdisciplinary approach has been proposed for chronic pelvic pain, where these multifactorial comorbidities can be addressed by different interventions at a single integrated center. Moreover, while cross-sectional studies can provide some insight into the association between these comorbidities and chronic pelvic pain severity, prospective longitudinal cohorts can identify comorbidities associated with changes in chronic pelvic pain severity over time.

OBJECTIVE:

We sought to describe trends and factors associated with chronic pelvic pain severity over a 1-year prospective cohort at an interdisciplinary center, with a focus on the role of comorbidities and controlling for baseline pain, demographic factors, and treatment effects.

STUDY DESIGN:

This was a prospective 1-year cohort study at an interdisciplinary tertiary referral center for pelvic pain and endometriosis, which provides minimally invasive surgery, medical management, pain education, physiotherapy, and psychological therapies. Exclusion criteria included menopause or age >50 years. Sample size was 296 (57% response rate at 1 year; 296/525). Primary outcome was chronic pelvic pain severity at 1 year on an 11-point numeric rating scale (0-10), which was categorized for ordinal regression (none-mild 0-3, moderate 4-6, severe 7-10). Secondary outcomes included functional quality of life and health utilization. Baseline comorbidities were endometriosis, irritable bowel syndrome, painful bladder syndrome, abdominal wall pain, pelvic floor myalgia, and validated questionnaires for depression, anxiety, and catastrophizing. Multivariable ordinal regression was used to identify baseline comorbidities associated with the primary outcome at 1 year.

RESULTS:

Chronic pelvic pain severity decreased by a median 2 points from baseline to 1 year (6/10-4/10, P < .001). There was also an improvement in functional quality of life (42-29% on the pain subscale of the Endometriosis Health Profile-30, P < .001), and a reduction in subjects requiring a physician visit (73-36%, P < .001) or emergency visit (24-11%, P < .001) in the last 3 months. On multivariable ordinal regression for the primary outcome, chronic pelvic pain severity at 1 year was independently associated with a higher score on the Pain Catastrophizing Scale at baseline (odds ratio, 1.10; 95% confidence interval, 1.00-1.21, P = .04), controlling for baseline pain, treatment effects (surgery), age, and referral status.

CONCLUSION:

Improvements in chronic pelvic pain severity, quality of life, and health care utilization were observed in a 1-year cohort in an interdisciplinary setting. Higher pain catastrophizing at baseline was associated with greater chronic pelvic pain severity at 1 year. Consideration should be given to stratifying pelvic pain patients by catastrophizing level (rumination, magnification, helplessness) in research studies and in clinical practice.

 

 

 

Am J Obstet Gynecol. 2017 Oct 13. pii: S0002-9378(17)31180-8.

Bowel endometriosis: diagnosis and management.   

Nezhat C¹, Li A², Falik R², Copeland D³, Razavi G⁴, Shakib A⁵, Mihailide C⁶, Bamford H⁷, DiFrancesco L⁸, Tazuke S⁹, Ghanouni P¹⁰, Rivas H¹⁰, Nezhat A¹, Nezhat C¹¹, Nezhat F¹².

 

Abstract

The most common location of extragenital endometriosis is the bowel. Medical treatment may not provide long-term improvement in patients who are symptomatic, and consequently most of these patients may require surgical intervention. Over the past century, surgeons have continued to debate the optimal surgical approach to treating bowel endometriosis, weighing the risks against the benefits. In this expert review we will describe how the recommended surgical approach depends largely on the location of disease, in addition to size and depth of the lesion. For lesions approximately 5-8 cm from the anal verge, we encourage conservative surgical management over resection to decrease the risk of short- and long-term complications.

 

 

 

J Minim Invasive Gynecol. 2017 Oct 13. pii: S1553-4650(17)31232-3.

Of Mice and Women: A Laparoscopic Mouse Model for Endometriosis.

Peterse D¹, Binda MM¹, O DF¹, Vanhie A¹, Fassbender A¹, Vriens J¹, D’Hooghe TM².

Abstract

STUDY OBJECTIVE:

To demonstrate how a novel laparoscopic approach allows the development of a mouse model for endometriosis after seeding menstrual endometrium from donor mice into the abdominal cavity of syngeneic recipient mice.

DESIGN:

A step-by-step video description of the techniques used to adapt the estrous cycle of mice towards a menstrual cycle and to subsequently induce endometriosis via laparoscopic seeding of menstrual endometrium.

SETTING:

University research institute.

ETHICS:

All animal experiments were ethically approved by KU Leuven, Belgium (ethical approval number: P031/2013).

INTERVENTIONS, MEASUREMENTS, AND MAIN RESULTS:

Oophorectomized female C57BL/6JRj mice received a series of estrogen injections. Next, a progesterone pellet was administered, together with a second series of estrogen injections. In addition, decidualization of the endometrium was induced with an intrauterine sesame oil stimulus. Four days later the progesterone pellet was removed and menstruation started [1]. Five hours after the progesterone pellet was removal the uterus was harvested, and the menstrual endometrium was dissected and seeded into the abdominal cavity of syngeneic recipient mice to induce endometriosis [2] using a laparoscopic approach [3]. Uterus and lesions were removed from the recipient mice 1 week after induction, and tissues were immunohistochemically stained for H&E, vimentin, and cytokeratin.

CONCLUSION:

In this video we show a novel methodology to induce endometriosis in mice using laparoscopic inoculation of syngeneic menstrual endometrium, mimicking Sampson’s theory of retrograde menstruation [4]. Compared with currently available rodent models, our model offers a less invasive and more physiologic way for fundamental and preclinical endometriosis research, with a high endometriosisincidence and lesion take rate.

 

 

 

J Minim Invasive Gynecol. 2017 Oct 12.

Comparison of Industry-Leading Energy Devices for Use in Gynecologic Laparoscopy: Articulating ENSEAL versus LigaSure Energy Devices.

Shiber LJ¹, Ginn DN², Jan A³, Gaskins JT⁴, Biscette SM³, Pasic R³.

Abstract

STUDY OBJECTIVE:

To compare 2 laparoscopic bipolar electrosurgical devices used in total laparoscopic hysterectomy (TLH). An articulating advanced bipolar device (ENSEAL G2; Ethicon Endo-Surgery, Cincinnati, OH) and an electrothermal bipolar vessel sealer (LigaSure; Medtronic, Minneapolis, MN) were analyzed for differences in surgeon perception of ease of instrument use and workload using the NASA Raw Task Load Index (RTLX) scale. A second objective was to examine differences in operative time, estimated blood loss (EBL), and perioperative complication rates between the 2 devices.

DESIGN:

Single-institution, single-blinded, randomized controlled trial (Canadian Task Force classification I).

SETTING:

Division of Minimally Invasive Gynecologic Surgery in a university hospital.

PATIENTS:

Eligibility required planned TLH, over age 18 years, and able to give informed consent; exclusions were stage III or IV endometriosis, known gynecologic malignancy, and early decision for conversion to laparotomy. One hundred seventy-eight patients screened, 142 enrolled, 2 withdrew, and 140 completed the study. Patients were followed 1 month postoperatively.

INTERVENTIONS:

Preoperative randomization to articulating advanced bipolar device or electrothermal bipolar vessel sealer to be used during TLH.

MEASUREMENTS AND MAIN RESULTS:

At the end of each hysterectomy the primary surgeon completed an ergonomic assessment tool, the RTLX. Results were analyzed to detect differences in workload between the 2 devices. For each case the time to ligation of the bilateral uterine arteries, EBL, and complications (including device failure, blood transfusion, or other injury) were recorded. Statistical analysis was performed using the t test for normally distributed data, χ² test for categorical data, and Mann-Whitney U-test for nonparametric data. There were no differences in age, body mass index, parity, prior surgery, uterine weight, race, indication, pathology, and comorbidities between the 2 groups. A statistically significant increase in RTLX scores (p < .0001), device failures (p = .0031), and time to ligation of bilateral uterine arteries (p = .0281) was noted in the articulating device group. No significant differences in EBL or complication rates were noted between the groups.

CONCLUSIONS:

The articulating advanced bipolar device was shown to have a statistically significant increase in surgeon-perceived workload and rate of device failure when used in TLH; however, clinical and surgical outcomes were equivalent.

 

 

 

Gynecol Oncol. 2017 Dec;147(3):642-647.

LINE-1 retrotransposon-mediated DNA transductions in endometriosisassociated ovarian cancers.

Xia Z¹, Cochrane DR², Anglesio MS³, Wang YK², Nazeran T¹, Tessier-Cloutier B¹, McConechy MK⁴, Senz J², Lum A², Bashashati A², Shah SP⁵, Huntsman DG⁶.

Abstract

OBJECTIVE:

Endometrioid (ENOC) and clear cell ovarian carcinoma (CCOC) share a common precursor lesion, endometriosis, hence the designation endometriosis associated ovarian cancers (EAOC). Long interspersed nuclear element 1 (LINE-1 or L1), is a family of mobile genetic elements activated in many cancers capable of moving neighboring DNA through 3′ transductions. Here we investigated the involvement of specific L1-mediated transductions in EAOCs.

METHODS:

Through whole genome sequencing, we identified active L1-mediated transductions originating within the TTC28 gene in 34% (10/29) of ENOC and 31% (11/35) of CCOC cases. We used PCR and capillary sequencing to assess the presence of specific TTC28-L1 transductions in formalin-fixed paraffin-embedded (FFPE) blocks from six different anatomical sites (five tumors and one normal control) for four ENOC and three CCOC cases, and compared the results to the presence of single nucleotide variations (SNVs)/frame shift (fs) mutations detected using multiplex PCR and next generation sequencing.

RESULTS:

TTC28-L1 mediated transductions were identified in at least three tumor samplings in all cases, and were present in all five tumor samplings in 5/7 (71%) cases. In these cases, KRAS, PIK3CA, CTNNB1, ARID1A, and PTEN mutations were found across all tumor sites while other selected SNV/fs mutations of unknown significance were present at varying allelic frequencies.

CONCLUSION:

The TTC28-L1 transductions along with classical driver mutations were near ubiquitous across the tumors, suggesting that L1 activation likely occurred early in the development of EAOCs. TTC28-L1 transductions could potentially be used to determine clonal relationships and to track ovarian cancer progression.

 

 

 

Case Rep Gastroenterol. 2017 Aug 23;11(2):494-499.

 

Preoperative Diagnosis of Intestinal Endometriosis by Magnifying Colonoscopy and Target Biopsy.

Tomiguchi J^1,2, Miyamoto H¹, Ozono K³, Gushima R¹, Shono T¹, Naoe H¹, Tanaka M¹, Baba H⁴, Katabuchi H⁵, Sasaki Y¹.

 

Abstract

Endometriosis can affect any portion of the gastrointestinal tract. A preoperative definitive diagnosis of intestinal endometriosis is difficult, because there is no characteristic endoscopic finding and the endoscopic biopsies usually sample insufficient endometrial tissue for pathologic diagnosis. To our knowledge, the magnifying endoscopic features of intestinal mucosal endometriosis have not been well documented. In this study, we report a case of intestinal endometriosis diagnosed preoperatively by magnifying image-enhanced colonoscopy and target biopsy. A 45-year-old woman was referred to our hospital with abdominal pain in the left lower quadrant. Colonoscopy showed a submucosal tumor-like lesion of approximately 30 mm in diameter exhibiting surface reddening and granular changes in the sigmoid colon. Magnifying endoscopy revealed sparsely distributed round pits in the granules. The mucosal biopsy specimen from the granule provided the diagnosis of intestinal endometriosis. Segmental sigmoidectomy was performed, and pathological examination revealed that the surface colonic mucosa was partially replaced by endometrial tissue, which accounted for the granular change detected in the colonoscopy. It can be speculated that the round pit might reflect the endometrial glands surrounded by endometrial stroma. This case illustrated the characteristic finding and utility of magnifying endoscopy for mucosal intestinal endometriosis.

 

 

 

Eur J Pain. 2017 Oct 16.

Bradykinin system is involved in endometriosis-related pain through endothelin-1 production.

Yoshino O¹, Yamada-Nomoto K¹, Kobayashi M¹, Andoh T², Hongo M¹, Ono Y¹, Hasegawa-Idemitsu A³, Sakai A², Osuga Y³, Saito S¹.

Abstract

BACKGROUND:

Endometriosis is a gynaecological disease exhibiting severe pelvic pain, but the mechanism of pain production remains unknown. Bradykinin (BK) is known as an inflammatory mediator, and shows elevated levels in inflammatory diseases such as rheumatoid arthritis. In the present study, we evaluated whether BK is involved in endometriosis-related pain.

METHODS:

Endometriotic lesions were used for immunohistochemistry. Primary cultures of endometriotic stromal cells (ESC) were stimulated with IL-1β and/or BK. Quantitative RT-PCR was used to evaluate the mRNA expressions of BK receptors (BKR) and endothelin-1 in ESC. The concentration of endothelin-1 in cystic fluid of endometrioma or non-endometrioma was measured with ELISA. The conditioned medium of ESC stimulated with IL-1β and/or BK was injected intraplantarly in mice, and evaluated whether pain-related licking behaviour was elicited.

RESULTS:

The expressions of BK and BKR in endometriotic lesions were observed by immunohistochemistry. In vitro experiments showed that IL-1β induced BKR-B1 and B2 on ESC. Activation of these receptors by BK significantly induced endothelin-1 expression in ESC, which was negated completely by HOE-140, a BKR-B2 antagonist. The cystic fluid of endometrioma contained higher amount of endothelin-1 compared to non-endometrioma. Intraplantar injection of the conditioned medium of ESC treated with IL-1β and BK significantly induced licking behaviour, which was suppressed with BQ-123, an endothelin type-A receptor antagonist.

CONCLUSIONS:

The present study demonstrated the presence and the function of the BK axis in endometriosis, and established a potential new therapy target for endometriosis-related pain.

SIGNIFICANCE:

The present study demonstrated (1) the presence and the function of the BK system in endometriosis, (2) activation of BKR induced endothelin-1 in endometriotic lesion and (3) blocking endothelin-1 was effective to decrease pain.

 

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Dec;219:28-34.

Use of the endometriosis fertility index in daily practice: A prospective evaluation.

Boujenah J¹, Cedrin-Durnerin I², Herbemont C³, Bricou A², Sifer C², Poncelet C³.

Abstract

OBJECTIVE:

To perform a prospective evaluation of postoperative fertility management using the endometriosis fertility index (EFI).

STUDY:

This prospective non-interventional observational study was performed from January 2013 to February 2016 in a tertiary care university hospital and an assisted reproductive technology (ART) centre. In total, 196 patients underwent laparoscopic surgery for endometriosis-related infertility. Indications for surgery included pelvic pain (dysmenorrhoea, and/or deep dyspareunia), abnormal hysterosalpingogram, and failure to conceive after three or more superovulation cycles with or without intra-uterine insemination. Multidisciplinary fertility management followed the surgical diagnosis and treatment of endometriosis. Three postoperative options were proposed to couples based on the EFI score: EFI score ≤4, ART (Option 1); EFI score 5-6, non-ART management for 4-6 months followed by ART (Option 2); or EFI score ≥7, non-ART management for 6-9 months followed by ART (Option 3). The main outcomes were non-ART pregnancy rates and cumulative pregnancy rates according to EFI score. Univariate and multivariate analyses with backward stepwise logistic regression were used to explain the occurrence of non-ART pregnancy after surgery for women with EFI scores ≥5. Adjustment was made for potential confounding variables that were significant (p<0.05) or tending towards significance (p<0.1) on univariate analysis.

RESULTS:

The cumulative pregnancy rate was 76%. The total number of women and pregnancy rates for Options 1, 2 and 3 were: 26 and 42.3%; 56 and 67.9%; and 114 and 87.7%, respectively. The non-ART pregnancy rates for Options 1, 2 and 3 were 0%, 30.5% and 48.2%, respectively. The ART pregnancy rates for Options 1, 2 and 3 were 50%, 60.6% and 80.3%, respectively. The mean time to conceive for non-ART pregnancies was 4.2 months. The benefit of ART was inversely correlated with the mean EFI score. On multivariate analysis, the EFI score was significantly associated with non-ART pregnancy (odds ratio 1.629, 95% confidence interval 1.235-2.150).

CONCLUSION:

In daily prospective practice, the EFI was useful for subsequent postoperative fertility management in infertile patients with endometriosis.