Ann Dermatol Venereol. 2017 Oct;144(10):617-620.

Umbilical endometriosis mimicking a keloid in a young black woman: A case report.

Kourouma HS1Ecra EJ2Allou AS2Kouyaté M2Kouassi YI2Kaloga M2Kouassi KA2Kassi K2Kouamé K2Ahogo C2Gbery IP2Sangaré A2.

 

Abstract

BACKGROUND:

Most umbilical tumors are diagnosed as benign tumors, umbilical metastases of abdominal and pelvic tumors, or Sister Marie Joseph nodule. Herein, we report a case of cutaneous umbilical endometriosismistaken for a keloid.

PATIENTS AND METHODS:

A young black woman aged 26 consulted for a painful umbilical tumefaction. She had noted the appearance of a nodule of the umbilicus 10 months ago with bleeding during her menstrual periods. Skin examination revealed a firm and painful umbilical nodule 2.5cm in diameter. She was treated with corticosteroid injections for one month for umbilical keloid. Given that the symptoms recurred regularly at the time of menstruation, we suspected umbilical endometriosis. This diagnosis was finally confirmed by histopathological examination and hormone therapy was instituted on gynecological advice before scheduled surgical excision.

CONCLUSION:

In a setting of an umbilical tumor simulating a keloid associated with cyclical symptoms in a black woman, the diagnosis of umbilical endometriosis should not be overlooked by the dermatologist.

 

 

J Manag Care Spec Pharm. 2017 Jul;23(7):745-754.

The Effect of Endometriosis Symptoms on Absenteeism and Presenteeism in the Workplace and at Home.

Soliman AM1Coyne KS2Gries KS3Castelli-Haley J1Snabes MC1Surrey ES4.

 

Abstract

BACKGROUND:

Characterized by pain symptoms, endometriosis affects women’s productivity in their prime working years.

OBJECTIVE:

To evaluate the effect of individual endometriosis symptoms on household chore and employment productivity as measured by presenteeism and absenteeism in a population survey of women with endometriosis.

METHODS:

An online survey of U.S. women was conducted to evaluate the prevalence of endometriosis, as well as symptoms, demographics, and clinical characteristics of the respondents. Women aged 18-49 years (inclusive) with endometriosis completed the Health-related Productivity Questionnaire to assess presenteeism and absenteeism for employed and household work. Descriptive statistics were used to describe the sample, survey responses, and the effect of endometriosis symptom severity on household chore and employment productivity. Regression analyses were performed to examine the effect of individual endometriosis symptoms on employment and household productivity lost because of presenteeism and absenteeism.

RESULTS:

Of 59,411 women who completed the prevalence screener, 5,879 women (9.9%) met the inclusion criteria for completing the survey; 1,318 women (2.2%) reported endometriosis and at least 1 hour of scheduled household chores in the past 7 days. Of these, 810 women had least 1 hour of scheduled employment in the past 7 days. Mean age was 34.6 years (standard error [SE] ± 0.32); 77.2% of the women were white; 59.3% were married or in a civil union; and 59.1% were employed full or part time. Women with endometriosis had a weekly loss of an average of 5.3 hours (SE ± 0.4) because of employment presenteeism, 1.1 hours (SE ± 0.2) of employment absenteeism, 2.3 (SE ± 0.2) hours of household presenteeism, and 2.5 (SE ± 0.2) hours of household absenteeism. Hourly losses in employment and household chore productivity were significantly greater with increasing symptom severity (mild vs. severe: 1.9 vs. 15.8 total employment hours lost and 2.5 vs. 10.1 total household hours lost; P < 0.0001). Women who experienced 3 endometriosis symptoms concurrently lost a significantly greater number of employment hours because of absenteeism and presenteeism compared with those experiencing 1 or 2 symptoms (P < 0.001). Regression analyses showed that a range of endometriosissymptoms predicted employment and household losses because of presenteeism and absenteeism.

CONCLUSIONS:

There was a significant relationship between the number and patient-reported severity of endometriosis symptoms experienced and hours of employment and household productivity lost because of presenteeism and absenteeism. Study findings indicate a need for guidance strategies to help women and employers manage endometriosis so as to reduce productivity loss.

DISCLOSURES:

The design and financial support for this study was provided by AbbVie. AbbVie participated in data analysis, interpretation of data, review, and approval of the manuscript. Coyne and Gries are employees of Evidera- Evidence, Value & Access by PPD and were paid scientific consultants for AbbVie in connection with this study. Soliman, Castelli-Hayley, and Snabes are AbbVie employees and may own AbbVie stock or stock options. Surrey is affiliated with Colorado Center for Reproductive Medicine and was paid by AbbVie as a consultant for this project. Surrey serves as a consultant for AbbVie outside of this project. All authors participated in data analysis and interpretation, and contributed to the development of the manuscript. The authors maintained control over the final contents of the manuscript and the decision to publish. Study concept and design were contributed by Soliman, Coyne, Gries, and Castelli-Haley. Soliman, Castelli-Haley, Coyne, and Gries collected the data, and data interpretation was performed by Snabes, Surrey, Soliman, Coyne, and Gries. The manuscript was written and revised by Soliman, Coyne, and Gries, along with the other authors.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Aug;215:215-219.

Aldo-keto reductase activity after diethylhexyl phthalate exposure in eutopic and ectopic endometrial cells.

Kim Y1Kim MR1Kim JH1Cho HH2.

 

Abstract

OBJECTIVE:

Endometriosis is a multifactorial gynaecological disease in reproductive-age women. Endometriotic tissue is characterized by high prostaglandin levels and progesterone resistance. Human aldo-keto reductases (AKRs) convert progesterone to a less potent metabolite and cause progesterone resistance. Therefore, in this study, we evaluated whether diethylhexyl phthalate (DEHP) alters AKR expression in human ectopic and eutopic endometrium.

STUDY DESIGN:

We used microarrays and western blotting to study the effects of DEHP, and checked the presence of AKR in endometriosis patients by enzyme-linked immunosorbent assay (ELISA).

RESULTS:

Cultured human endometrial cells from normal endometrium of women without endometriosis (NE), eutopic endometrium from endometriosis patients (EE), and ectopic endometrium from endometriosis patients (EC) differed in genetic expression changes after DEHP treatment. DEHP upregulated AKR1C1, AKR1C2, AKR1C3, and AKR1B10 expression in EE, while EC showed continuously increased AKR1C3 expression before and after DEHP exposure. In western blot analysis, before and after DEHP exposure, the AKR1B10 protein band was detected in NE, EE, and EC, whereas the AKR1C3 band was detected only in EC. AKR1B10 and AKR1C3 expression levels in the blood of the enrolled patients were evaluated using ELISA. AKR1B10 expression did not differ between groups (without endometriosis [N=13], 0.10 vs. with endometriosis [N=20], 0.11; P=0.27). AKR1C3 expression was significantly higher in the blood of endometriosis patients than in that of patients without endometriosis (without endometriosis, 9.1 vs. with endometriosis, 10.1; P=0.02). Analysis according to menstrual period showed significantly increased AKR1C3 levels in patients with endometriosis only during the secretory phase and not the proliferative phase (P<0.05).

CONCLUSION:

DEHP induces AKR activity in the endometrium of endometriosis patients, and AKR1C3 might influence the development of endometriosis.

 

 

Eur J Obstet Gynecol Reprod Biol. 2017 Aug;215:220-223.

Incidence of ovarian endometrioma among women with peritoneal endometriosis with and without a history of hormonal contraceptive use.

Kavoussi SK1Odenwald KC2As-Sanie S3Lebovic DI4.

 

Abstract

OBJECTIVE(S):

To determine if, among women with peritoneal endometriosis, the incidence of ovarian endometrioma at first laparoscopy differs between those with and without a history of hormonal contraceptive use.

STUDY DESIGN:

Retrospective case-control study of women who were patients at a fertility center and had first laparoscopy from 2009 through 2015 showing, at minimum, evidence of peritoneal endometriosis (n=136). Chart review was conducted for history of prior birth control use as well as operative and pathology notes of surgeries. Study subjects were grouped as follows: women with peritoneal endometriosis diagnosed by laparoscopy who had a history of hormonal contraceptive use (n=93) and women with peritoneal endometriosis diagnosed by laparoscopy who had never used hormonal contraceptives (n=43). The main outcome measure was the incidence of ovarian endometrioma among women with peritoneal endometriosis who had a history of hormonal contraceptive use as compared to women with peritoneal endometriosis who had a history of no hormonal contraceptive use.

RESULTS:

Among women with peritoneal endometriosis who had a history of hormonal contraceptive use, 17/93 (18.3%) were found to have endometriomas. Among women with peritoneal endometriosis who had a history of no hormonal contraceptive use, 21/43 (48.8%) were found to have endometriomas. The chi-square statistic was 13.6 (P-value<0.001).

CONCLUSION(S):

Among women with peritoneal endometriosis, those with a history of hormonal contraceptive use had a lower incidence of ovarian endometrioma than those with a history of no hormonal contraceptive use. Possible mechanisms of action include reducing the risk of a corpus luteum formation and subsequent transformation into an ovarian endometrioma or reducing the risk of ectopic endometrium implantation into the ovary via the diminution of retrograde menstruation. Although larger, prospective studies are needed, the findings of this study suggest that the use of hormonal contraception may decrease the likelihood of ovarian endometrioma formation among women with peritoneal endometriosis.

 

 

Biochim Biophys Acta. 2017 Sep;1863(9):2282-2292.

Challenges in endometriosis miRNA studies – From tissue heterogeneity to disease specific miRNAs.

Saare M1Rekker K2Laisk-Podar T2Rahmioglu N3Zondervan K4Salumets A5Götte M6Peters M2.

 

Abstract

In order to uncover miRNA changes in endometriosis pathogenesis, both endometriotic lesions and endometrial biopsies, as well as stromal and epithelial cells isolated from these tissues have been investigated and a large number of dysregulated miRNAs have been reported. However, the concordance between the result of different studies has remained small. One potential explanation for limited overlap between the proposed disease-related miRNAs could be the heterogeneity in tissue composition, as some studies have compared highly heterogeneous whole-lesion biopsies with endometrial tissue, some have compared the endometrium from patients and controls, and some have used pure cell fractions isolated from lesions and endometrium. This review focuses on the results of published miRNA studies in endometriosis to reveal the potential impact of tissue heterogeneity on the discovery of disease-specific miRNA alterations in endometriosis. Additionally, functional studies that explore the roles of endometriosis-involved miRNAs are discussed.

 

 

Fertil Steril. 2017 Aug;108(2):284-288.

Patients with endometriosis have aneuploidy rates equivalent to their age-matched peers in the in vitro fertilization population.

Juneau C1Kraus E2Werner M3Franasiak J4Morin S4Patounakis G5Molinaro T3de Ziegler D6Scott RT4.

 

Abstract

OBJECTIVE:

To determine whether endometriosis ultimately results in an increased risk of embryonic aneuploidy.

DESIGN:

Retrospective cohort.

SETTING:

Infertility clinic.

PATIENT(S):

Patients participating in an in vitro fertilization (IVF) cycle from 2009-2015 using preimplantation genetic screening (PGS) who had endometriosis identified by surgical diagnosis or by ultrasound findings consistent with a persistent space-occupying disease whose sonographic appearance was consistent with endometriosis.

INTERVENTION(S):

None.

MAIN OUTCOME MEASURE(S):

Rate of aneuploidy in endometriosis patients undergoing IVF compared to controls without endometriosis undergoing IVF.

RESULT(S):

There were 305 patients with endometriosis who produced 1,880 blastocysts that met the criteria for inclusion in the endometriosis group. The mean age of the patients with endometriosis was 36.1 ± 3.9 years. When the aneuploidy rates in patients with endometriosis and aneuploidy rates in patients without endometriosiswere stratified by Society for Assisted Reproductive Technology age groups and compared, there were no statistically significant differences in the rate of aneuploidy (odds ratio 0.85; 95% confidence interval, 0.84-0.85).

CONCLUSION(S):

Patients with endometriosis undergoing IVF have aneuploidy rates equivalent to their age-matched peers in IVF population who do not have endometriosis.

 

 

Evid Based Complement Alternat Med. 2017;2017:6489427.

Ping-Chong-Jiang-Ni Formula Induces Apoptosis and Inhibits Proliferation of Human Ectopic Endometrial Stromal Cells in Endometriosis via the Activation of JNK Signaling Pathway.

Liang RN1Li PS2Zou Y3Liu YL2Jiang Z4Liu Z5Fan P6Xu L6Peng JH1Sun XY1.

 

Abstract

Endometriosis is a common gynecological condition in childbearing age women and its therapy in modern medicine achieves usually temporary cure. Ping-Chong-Jiang-Ni formula (PCJNF), a Chinese herbal medicine (CHM), was shown to be clinically effective on endometriosis. Meanwhile, c-Jun N-terminal kinase (JNK) signaling pathway was involved in the therapeutic process of CHM on endometriosis. Here, we explored the effect of PCJNF on the ectopic endometrial stromal cells (EESCs) from endometriosis and test whether JNK signaling was involved. After being treated with PCJNF-containing serum obtained from Sprague Dawley rat, cell proliferation, migration, invasion, and apoptosis were evaluated in EESCs, and the total and phosphorylated JNK, ERK, and p38 proteins were detected. Our results showed that PCJNF could suppress cell proliferation, migration, and invasion and induce apoptosis in EESCs. The suppressed proliferation and increased apoptosis were dependent on JNK activation. Additionally, PCJNF caused cell cycle arrest at G2/M phase and this effect was mediated by JNK signaling, while the decreased cell migration and invasion treated by PCJNF were independent of JNK signaling. In summary, our results provided the first evidence that PCJNF could suppress cell proliferation, migration, and invasion, while increasing apoptosis in EESCs, and the suppressed proliferation and enhanced apoptosis were mediated by JNK signaling.

 

 

Reprod Sci. 2017 Jan 1:1933719117715126.

Pain Mechanisms in Peritoneal Diseases Might Be Partially Regulated by Estrogen.

Börner C1Scheerer C1Buschow R1Chiantera V1Sehouli J1Mechsner S1.

 

Abstract

To identify factors influencing the differential pain pathogenesis in peritoneal endometriosis (pEM) and peritoneal carcinomatosis in ovarian cancer (pOC), we undertook an experimental study. Tissue samples of 18 patients with pEM, 15 patients with pOC, and 15 unaffected peritoneums as controls were collected during laparoscopy or laparotomy. Immunohistochemical stainings were conducted to identify nerve fibers and neurotrophins in the tissue samples. Additionally, 23 pEM fluids, 25 pOC ascites fluids, and 20 peritoneal fluids of patients with myoma uteri as controls were collected. In these fluids, the expression of neurotrophins was evaluated. The effects of peritoneal fluids and ascites on the neurite outgrowth of chicken sensory ganglia were estimated by using a neuronal growth assay. An electrochemiluminescence immunoassay was carried out to determine the expression of estrogen in the peritoneal fluids and ascites. The total and sensory nerve fiber density was significantly higher in pEM than in pOC ( P < .001 and P < .01). All neurotrophins tested were present in tissue and fluid samples of pEM and pOC. Furthermore, the neurotrophic properties of pEM and pOC fluids were demonstrated, leading to sensory nerve fiber outgrowth. Estrogen concentration in the peritoneal fluids of pEM was significantly higher compared to ascites of pOC ( P < .001). The total and sensory nerve fiber density in the tissue samples as well as the estrogen expression in the peritoneal fluid of pEM was considerably higher than that in pOC, representing the most notable difference found in both diseases. This might explain the differential pain perception in pEM and pOC. Therefore, estrogen might be a key factor in influencing the genesis of pain in endometriosis.

 

Reprod Sci. 2017 Jan 1:1933719117715123

Upregulation of Interleukin 35 in Patients With Endometriosis Stimulates Cell Proliferation.

Zhang C1Peng Z1Ban D1Zhang Y1.

 

Abstract

In this study, we investigated the expression of interleukin 35 (IL-35) and its receptors in endometriosis, analyzed the function of IL-35 in primary culture model of endometrial stromal cells (ESCs), and evaluated their clinicapathological significance. Peripheral blood (PB) and peritoneal fluid (PF) were collected from 37 women with endometriosis and 24 control women. The ectopic endometrium was obtained from patients with endometriosis undergoing laparoscopic surgery. The eutopic and normal endometrium were collected by endometrial biopsy. Levels of IL-35 in PB and PF were evaluated by enzyme-linked immunosorbent assay. Women with endometriosis had higher levels of IL-35 compared to controls both in PB and in PF. Levels of n IL-35 were increased in patients with advanced stage endometriosis compared to those with early stages in PF. A significant upregulation of IL-35 was observed in patients with ovarian endometriosis accompanied with pelvic implants (PI) compared to those without PI in PB and PF. The relative messenger RNA and protein expression of EBi3 and p35, the subunits of IL-35, were significantly higher in ectopic endometrium than in eutopic and healthy endometrium as measured by immunohistochemistry and quantitative polymerase chain reaction. The ESCs from endometriosis displayed a remarkable overexpression of IL-35 receptor subunits, IL12Rβ2 and gp130, compared to those from controls . Moreover, recombined human IL-35 protein stimulated the upregulation of IL12Rβ2 and gp130 and facilitated proliferation of ESCs. Our study provides the first evidence that IL-35 was involved in the pathogenesis of endometriosis through suppressing immunoreaction and promoting proliferation of ESCs. IL-35 may potentially serve as a biomarker for endometriosis.

 

 

BMJ Case Rep. 2017 Jun 28;2017.

Insidious perforation of the rectum by a fallopian tube: the need to keep ‘an open mind’ when dealing with deep infiltrating endometriosis (DIE).

Marujo AT1Abreu B2Nogueira B3Reis J3.

 

Abstract

Endometriosis is a benign chronic disease which can have different degrees of severity and can potentially affect any organ. Intestinal endometriosis occurs in 3%—37% of the cases, being more frequent in the rectosigmoid transition. Transmural involvement of intestinal endometriosis is extremely rare and is usually associated with recurrent abdominal pain. Due to the cyclical hormone influence, endometriosis implants may infiltrate the deeper layers of the intestinal wall and may lead to bowel obstruction or perforation. We present a case of transmural perforation of the rectum wall by an adjacent organ (left fallopian tube) that occurred insidiously in a patient with deep infiltrative endometriosis. A complete set of images is presented, regarding the preoperative, intraoperative and postoperative findings.

 

 

Biomed Res Int. 2017;2017:9857196.

How to Use CA-125 More Effectively in the Diagnosis of Deep Endometriosis.

Oliveira MAP1Raymundo TS1Soares LC1Pereira TRD1Demôro AVE1.

 

Abstract

Deep infiltrative endometriosis (DIE) is a severe form of the disease. The median time interval from the onset of symptoms to diagnosis of endometriosis is around 8 years. In this prospective study patients were divided into two groups: cases (34 DIE patients) and control (20 tubal ligation patients). The main objective of this study was to evaluate the performance of CA-125 measurement in the menstrual and midcycle phases of the cycle, as well as the difference in its levels between the two phases, for the early diagnosis of DIE. Area Under the Curve (AUC) of CA-125 in menstrual phase and of the difference between menstrual and midcycle phases had the best performance (both with AUC = 0.96), followed by CA-125 in the midcycle (AUC = 0.89). The ratio between menstrual and midcycle phases had the worst performance. CA-125 may be useful for the diagnosis of deep endometriosis, especially when both are collected during menstruation and in midcycle. These may help to decrease the long interval until the definitive diagnosis of DIE. Multicentric studies with larger samples should be performed to better evaluate the cost-effectiveness of measuring CA-125 in two different phases of the menstrual cycle.

 

 

J Laparoendosc Adv Surg Tech A. 2017 Dec;27(12):1245-1250.

Laparoscopic Findings Associated with Bladder Endometriosis Are Correlated with Disease Severity.

Bouaziz J1Dotan Z2Zajicek M1Zolti M1Carp H1Goldenberg M1Seidman DS1Soriano D1.

 

Abstract

STUDY OBJECTIVE:

Bladder involvement is rare in endometriosis. The prevalence is estimated to be ∼1% in patients with endometriosis. However, this figure seems to be an underestimation. The diagnosis of bladder endometriosis might be missed during laparoscopy. The aim of this study was to determine an intraoperative visual score of pelvic lesions that help the surgeon suspect bladder endometriosis. Design, Design Classification: A retrospective analysis was performed on the intraoperative photographs and videos of 69 patients with histological confirmation of bladder endometriosis.

SETTING:

A tertiary referral center.

PATIENTS:

Sixty-nine patients with bladder endometriosis were operated on in our center over a 9-year period.

INTERVENTIONS:

Evaluation and analysis of intraoperative laparoscopic findings.

MAIN RESULTS:

We found three subtypes of laparoscopic findings that can assist with diagnosing bladder endometriosis. The most prominent sign was named “kissing round ligaments” (Type K), in which the right and left round ligaments appear closer to each other than usual or even touching one another. This sign is strongly associated with full-thickness invasion of the bladder. Other laparoscopic findings that indicated bladder endometriosis were anatomical distortion (Type A) and proximal occlusion of the tubes (Type B). We further define a scoring system for the lesion that correlates with the severity of the bladder endometriosis from superficial lesions to full thickness.

CONCLUSION:

Bladder endometriosis is a rare condition and often remains undiagnosed. Indeed, even during surgery, bladder endometriosis can be missed if the operator is not aware of the suggestive signs. Operative laparoscopic findings may help the surgeon to diagnose bladder endometriosis, and these signs correlate with the severity of the disease.

 

 

Comp Med. 2017 Jun 1;67(3):277-280.

Abdominal Wall Endometriosis in a Rhesus Macaque (Macaca mulatta).

Atkins HM1Caudell DL1Hutchison AR1LeGrande AC1Kock ND2.

 

Abstract

Endometriosis is the presence of endometrium outside of the uterus. Although endometriosis occurs in both pelvic and extrapelvic locations, extrapelvic locations are less common. The development of abdominal wall or incisional endometriosis in women is associated with gynecologic surgeries and is often misdiagnosed. Because they naturally develop endometriosis similar to women, Old World NHP, including rhesus macaques, provide excellent opportunities for studying endometriosis. Here, we describe a case of abdominal wall endometriosis in a rhesus macaque that had undergone cesarean section. Microscopically, the tissue consisted of pseudocolumnar epithelium-lined glands within a decidualized stroma, which dissected through the abdominal wall musculature and into the adjacent subcutaneous tissue. The stroma was strongly positive for vimentin and CD10 but was rarely, weakly positive for estrogen receptors and negative for progesterone. Close examination of extrapelvic endometriosis in rhesus macaques and other NHP may promote increased understanding of endometriosis in women.

 

 

Arch Gynecol Obstet. 2017 Jun 29. doi: 10.1007/s00404-017-4442-5.

Efficacy of dienogest in improving pain in women with endometriosis: a 12-month single-center experience.

Maiorana A1Incandela D2Parazzini F3,4Alio W1Mercurio A1Giambanco L1Alio L1.

 

Abstract

PURPOSE:

Dienogest has recently been marketed as a medical treatment for endometriosis. Given the recent introduction on the market of Dienogest, little data are available regarding its effectiveness in routine clinical practice.

METHODS:

The study is an observational, single-center, cohort study. Eligible was women with a surgical diagnosis of endometriosis dating back <24 months or a clinical/instrumental diagnosis of endometriosis and endometriosis-associated pelvic pain score of at least 40 mm on a 100-mm visual analog scale (VAS) at start of treatment and who had been taking Dienogest 2 mg once daily treatment at the time of study entry for no more than 30 days, consecutively observed between September 2013 to September 2014. In accordance with routine practice, women came back for clinical assessment and evaluation of pain after 1 (V1), 3 (V2), and 12 (V3) months.

RESULTS:

A total of 132 women were enrolled in the study. A total of 21 of the enrolled patients were released from the study during follow-up due to adverse effects. The mean pelvic pain VAS score at baseline was 8.9 (SD 1.3). The corresponding values were 6.7 (SD 3.2) and 5.7 (SD 3.7) for dyspareunia and dyschezia. The mean VAS scores progressively and significantly decreased to 0.9 (SD 1.6) for pelvic pain, 1.4 (SD 2.1) for dyspareunia and 0.2 (SD 0.9) for dyschezia, respectively, 12 months after start of treatment.

CONCLUSION:

This study confirms that in routine clinical practice, Dienogest 2 mg is an effective and well-tolerated treatment for endometriosis-related pain in women with endometriosis.

 

 

Arch Gynecol Obstet. 2017 Jun 29. doi: 10.1007/s00404-017-4448

“Per vaginam” topical use of hormonal drugs in women with symptomatic deep endometriosis: a narrative literature review.

Buggio L1Lazzari C2Monti E2Barbara G2Berlanda N2Vercellini P2.

 

Abstract

PURPOSE:

We aim to provide a comprehensive overview of the role of the vagina as a route for drug delivery and absorption, with a particular focus on the use of vaginal hormonal compounds for the treatment of deep infiltrating symptomatic endometriosis.

METHODS:

A MEDLINE search through PubMed was performed to identify all published studies in English language on vaginal hormonal treatments for symptomatic endometriosis.

RESULTS:

Main advantages of the vaginal route include avoidance of the hepatic-first pass metabolic effect, the possibility of using lower therapeutic dosages, and the reduction of side effects compared with the oral administration. Studies on endometriosis treatment mainly focused on the use of vaginal danazol (n = 6) and the contraceptive vaginal ring (n = 2). One pilot study evaluated the efficacy of vaginal anastrozole in women with rectovaginal endometriosis. Most investigations evaluated the vaginal use of hormonal agents in women with deep infiltrating endometriosis/rectovaginal endometriosis. Overall, a substantial amelioration of pelvic pain symptoms associated with endometriosis was observed, particularly of dysmenorrhea. A significant reduction in rectovaginal endometriotic nodule dimensions measured at ultrasound examination was detected by some but not all authors.

CONCLUSIONS:

The vaginal route represents a scarcely explored modality for drug administration. High local hormonal concentrations might achieve a greater effect on endometriotic lesions compared with alternative routes. Future studies should focus on the use of the vagina for delivering target therapies particularly in patients with deeply infiltrating rectovaginal lesions.

 

 

Fertil Steril. 2017 Jul;108(1):28-31.

Endometrial receptivity in eutopic endometrium in patients with endometriosis: it is not affected, and let me show you why.

Miravet-Valenciano J1Ruiz-Alonso M1Gómez E1Garcia-Velasco JA2.

 

Abstract

Many women with endometriosis experience compromised fertility. This disease clearly exerts quantitative damage on the ovaries, and perhaps, also qualitative damage. However, it remains controversial whether endometrial receptivity is compromised. Here we review the evidence from basic transcriptomic signature data to clinical data from an oocyte donation model and find support for the concept that endometrial receptivity is not impaired in women with endometriosis when healthy embryos reach the endometrial cavity.

 

 

Reprod Sci. 2018 Feb;25(2):207-213

Overexpression of Four Joint Box-1 Protein (FJX1) in Eutopic Endometrium From Women With Endometriosis.

Chang HJ1,2Yoo JY1Kim TH1Fazleabas AT1Young SL3Lessey BA4Jeong JW1.

 

Abstract

The four jointed box 1 (FJX1) is a regulator of angiogenesis, and the levels of FJX1 are increased in several types of cancer. Angiogenesis plays a critical role in endometrial growth as well as in several gynecologic disorders including endometriosis. However, the function of FJX1 has not been studied in endometriosis. Therefore, we examined the levels of FJX1 in eutopic endometrium from women with or without endometriosis. The levels of FJX1 protein did not change in endometrial cells during the menstrual cycle in endometrium from women without endometriosis. However, its levels were significantly higher in the secretory phase of the eutopic endometrium from women with endometriosis when compared to women without endometriosis. Hypoxia-inducible factor-1α (HIF1α) is known as a key mediator of endometriosis by regulating genes essential to estrogen production, angiogenesis, proliferation, inflammation, and extracellular invasion. It has been reported that FJX1 induces an increase in HIF1α through posttranslational stabilization. The results of our Western blot analysis reveal a significant positive correlation between FJX1 and HIF1α proteins in endometrium of women with and without endometriosis. This overexpression of FJX1 was confirmed by sequential analysis of the eutopic endometrium during endometriosis progression, using an induced model of endometriosis in the baboon. Therefore, our results suggest that high levels of FJX1 proteins may play an important role in the pathogenesis of endometriosis.

 

 

Gynecol Oncol. 2017 Sep;146(3):609-614.

Prognostic impact of interleukin-6 expression in stage I ovarian clear cell carcinoma.

Kawabata A1Yanaihara N2Nagata C3Saito M1Noguchi D4Takenaka M1Iida Y1Takano H4Yamada K1Iwamoto M5Kiyokawa T5Okamoto A1.

 

Abstract

OBJECTIVE:

Ovarian clear cell carcinoma (OCCC) frequently presents at an early stage. In stage I OCCC, the prognosis differs according to substage. In particular, predictive biomarkers and new treatment strategies are needed for stage IC2/IC3 disease. We investigated tumor biology and prognostic factors for stage I OCCC from a clinicopathological perspective, including the expression of ARID1A and IL-6, which are considered critical for OCCC carcinogenesis.

METHODS:

A retrospective cohort study of 192 patients with stage I OCCC treated at a single institution was performed. We calculated overall survival (OS) with respect to 12 clinicopathological parameters that included the unique and diverse histological features of OCCC.

RESULTS:

The estimated 5-year OS rate in patients with all stage I OCCC was 88.9% during a median of 91months of follow-up. The multivariate analysis indicated that substage classification and IL-6 expression status were associated with poor OS (p=0.010 and p=0.027, respectively). Loss of ARID1A expression had no impact on survival; however, it was associated with substage (p=0.001), capsule rupture status (p=0.011), and ascites cytology (p=0.016). No clear association was found between ARID1A and IL-6 expressions. Histological findings, including the presence of endometriosis, adenofibroma, architectural pattern, and tumor cell type, showed no prognostic effects.

CONCLUSIONS:

Both substage classification and IL-6 expression status may be independent prognostic factors in stage I OCCC. Therefore, IL-6 molecular stratification may be crucial in optimizing therapeutic strategies for early stage OCCC to improve survival.

 

 

J Minim Invasive Gynecol. 2017 Nov – Dec;24(7):1145-1151.

Bowel Preparation Improves the Accuracy of the Transvaginal Ultrasound in the Diagnosis of Rectosigmoid Deep Infiltrating Endometriosis: a Prospective Study.

Ros C1Martínez-Serrano MJ2Rius M2Abrao MS3Munrós J2Martínez-Zamora MÁ2Gracia M2Carmona F2.

 

Abstract

STUDY OBJECTIVE:

To compare the accuracy of transvaginal ultrasound (TVUS) with and without bowel preparation (BP) to detect and describe intestinal nodules of deep infiltrating endometriosis (DIE) with laparoscopic findings.

DESIGN:

prospective study of paired data. DESIGN CLASSIFICATION: type II.1 SETTING: tertiary university hospital from November 2014 to November 2015.

PATIENTS:

a cohort of women awaiting surgery for endometriosis.

INTERVENTIONS:

The wall of the rectum and lower sigmoid colon of the patients was evaluated by 2 TVUS: the first ultrasound was performed without previous BP and the second was done after a three-day low-residue diet and two 250 ml enemas 12h and 3h before TVUS.

MEASUREMENTS:

The presence or absence of rectosigmoid nodules visualized by TVUS with and without BP were compared with laparoscopic results.

MAIN RESULTS:

Forty patients with a mean age of 36.8±5.0 years were included in the study. On comparing the surgical findings histologically confirmed (presence or absence of bowel nodules and localization) with those of the two TVUS with and without BP, the sensitivity, specificity and Cohen’s kappa (k) were 100%, 96% and k=0.95; and 73%, 88% and k=0.61, respectively. Laparoscopy showed that up to 37.5% of patients (15/40) presented bowel involvement. Variables were clearly more evaluable with than without BP.

CONCLUSIONS:

TVUS with BP has a higher accuracy than TVUS without BP. BP allows and facilitates the detection of more rectal nodules of DIE in patients with suspected endometriosis and surgical criteria.

 

 

Eur Radiol. 2017 Dec;27(12):5215-5224.

Evaluation of Mayer-Rokitansky-Küster-Hauser syndrome with magnetic resonance imaging: Three patterns of uterine remnants and related anatomical features and clinical settings.

Wang Y1Lu J2Zhu L3Sun Z4Jiang B1Feng F1Jin Z1.

 

Abstract

OBJECTIVE:

To characterize the anatomical features and clinical settings of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and correlate them with patterns of uterine involvement.

METHODS:

Pelvic magnetic resonance images and medical records of 92 MRKH patients were retrospectively reviewed. Patients were subgrouped by uterine morphology: uterine agenesis, unilateral rudimentary uterus and bilateral rudimentary uteri. Uterine volume, presence of endometrium, location of ovary, endometriosis and pelvic pain were compared among groups.

RESULTS:

The mean uterine volume was 33.5 ml (17.5-90.0 ml) for unilateral uterine remnants, and 16.1 ml (3.5-21.5 ml) for bilateral uterine rudiments (p<0.01). The incidence of presence of endometrium (100% vs. 22%, p<0.001), haematometra (56% vs. 3%, p<0.001) and ovarian endometriosis (22% vs. 3%, p<0.01) was significantly increased in the group of unilateral rudimentary uteri as compared with the group of bilateral uterine remnants. Thirty-one patients (38%) showed ectopic ovaries. Pelvic pain was more common in individuals with unilateral rudimentary uterus than those who had no (56% vs. 5%, p<0.01) or bilateral uterine remnants (56% vs. 14%, p<0.05).

CONCLUSION:

MRKH patients with different patterns of uterine involvement may have differentiated anatomical features and clinical settings.

KEY POINTS:

  • Rudimentary uteri, especially bilateral rudimentary uteri, were quite common in MRKH syndrome. • Uterine remnants can be relatively large, especially the unilateral rudimentary uterus. • Presence of endometrium and related complications are not rare in MRKH syndrome. • Existence of endometrium and complications are more frequent in unilateral rudimentary uterus.

 

 

 

J Endocrinol. 2017 Sep;234(3):269-278.

TNFRp55 deficiency promotes the development of ectopic endometriotic-like lesions in mice.

Vallcaneras S1Ghersa F1Bastón J2Delsouc MB1Meresman G2Casais M3.

 

Abstract

Endometriosis is an inflammatory disease depending on estradiol, with TNF-α being one of the most representative cytokines involved in its pathogenesis. TNF-α acts through its bond to the TNFRp55 and TNFRp75 membrane receptors. The aim of this study was to analyze the effect of the TNFRp55 deficiency on the development of ectopic endometriotic-like lesions. Endometriosis was induced surgically in mice of the C57BL/6 strain, wild type (WT) and TNFRp55-/- (KO). After four weeks, the peritoneal fluid was collected and the lesions were counted, measured with a caliper, removed, weighed, fixed or kept at -80°C. We evaluated the cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry and apoptosis by TUNEL technique in the ectopic lesions. MMP-2 and MMP-9 activities (factors involved in invasiveness) were measured by zymography in the peritoneal fluid; estradiol and progesterone levels were measured by radioimmunoassay in the lesions and in the peritoneal fluid. We found that in KO animals the mean number of lesions established per mouse, the lesion volume, weight and cell proliferation increased and apoptosis decreased. In addition, the activity of MMP-2 and the estradiol level increased, whereas the progesterone level was not significantly modified. In conclusion, the deficiency of TNFRp55 promoted the establishment and development of endometriosis through an increase in the lesion size and high levels of estradiol which correlate with an increase in the MMP-2 activity. This is evidence of the possible association of the deregulation of the TNFRp55 expression and the survival of the endometriotic tissue in ectopic sites.

 

 

J Pathol. 2017 Sep;243(1):26-36.

Clear cell and endometrioid carcinomas: are their differences attributable to distinct cells of origin?

Cochrane DR1Tessier-Cloutier B2Lawrence KM1Nazeran T2Karnezis AN1,2Salamanca C1Cheng AS1McAlpine JN3Hoang LN2,4Gilks CB2,4Huntsman DG1,2,3,4.

 

Abstract

Endometrial epithelium is the presumed tissue of origin for both eutopic and endometriosis-derived clear cell and endometrioid carcinomas. We had previously hypothesized that the morphological, biological and clinical differences between these carcinomas are due to histotype-specific mutations. Although some mutations and genomic landscape features are more likely to be found in one of these histotypes, we were not able to identify a single class of mutations that was exclusively present in one histotype and not the other. This lack of genomic differences led us to an alternative hypothesis that these cancers could arise from distinct cells of origin within endometrial tissue, and that it is the cellular context that accounts for their differences. In a proteomic screen, we identified cystathionine γ-lyase (CTH) as a marker for clear cell carcinoma, as it is expressed at high levels in clear cell carcinomas of the ovary and endometrium. In the current study, we analysed normal Müllerian tissues, and found that CTH is expressed in ciliated cells of endometrium (both eutopic endometrium and endometriosis) and fallopian tubes. We then demonstrated that other ciliated cell markers are expressed in clear cell carcinomas, whereas endometrial secretory cell markers are expressed in endometrioid carcinomas. The same differential staining of secretory and ciliated cells was demonstrable in a three-dimensional organoid culture system, in which stem cells were stimulated to differentiate into an admixture of secretory and ciliated cells. These data suggest that endometrioid carcinomas are derived from cells of the secretory cell lineage, whereas clear cell carcinomas are derived from, or have similarities to, cells of the ciliated cell lineage. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

 

 

Braz J Med Biol Res. 2017 Jul 3;50(7):e5782

Increased expression of ID2, PRELP and SMOC2 genes in patients with endometriosis.

Araujo FM1Meola J1Rosa-E-Silva JC1Paz CCP2Ferriani RA1Nogueira AA1.

 

Abstract

Endometriosis is a benign, estrogen-dependent disease with symptoms such as pelvic pain and infertility, and it is characterized by the ectopic distribution of endometrial tissue. The expression of the ID2, PRELP and SMOC2 genes was compared between the endometrium of women without endometriosis in the proliferative phase of their menstrual cycle and the eutopic and ectopic endometrium of women with endometriosis in the proliferative phase. Paired tissue samples from 20 women were analyzed: 10 from endometrial and peritoneal endometriotic lesions and 10 from endometrial and ovarian endometriotic lesions. As controls, 16 endometrium samples were collected from women without endometriosis in the proliferative phase of menstrual cycle. Analysis was performed by real-time polymerase chain reaction (PCR). There was no significant difference between gene expression in the endometrium of women with and without endometriosis. The ID2 gene expression was increased in the most advanced stage of endometriosis and in ovarian endometriomas, the PRELP was more expressed in peritoneal lesions, and the SMOC2 was highly expressed in both peritoneal and endometrioma lesions. Considering that the genes studied participate either directly or indirectly in cellular processes that can lead to cell migration, angiogenesis, and inappropriate invasion, it is possible that the deregulation of these genes caused the development and maintenance of ectopic tissue.

 

Am J Reprod Immunol. 2017 Nov;78(5). doi: 10.1111/aji.12726.

Increased expression of resistin in ectopic endometrial tissue of women with endometriosis.

Oh YK1Ha YR1Yi KW1Park HT1Shin JH1Kim T1Hur JY1.

 

Abstract

PROBLEM:

Inflammation is a key process in the establishment and progression of endometriosis. Resistin, an adipocytokine, has biological properties linked to immunologic functions, but its role in endometriosis is unclear.

METHOD OF STUDY:

Resistin gene expression was examined in eutopic and ectopic endometrial tissues from women with (n=25) or without (n=25) endometriosis. Resistin mRNA and protein levels were determined in endometrial tissue using quantitative real-time reverse transcription PCR and Western blotting, following adipokine profiling arrays.

RESULTS:

Resistin protein was detected in human endometrial tissues using an adipokine array test. Resistin mRNA and protein levels were significantly higher in ectopic endometrial tissue of patients with endometriosisthan in normal eutopic endometrial tissue.

CONCLUSION:

Our results indicate that resistin is differentially expressed in endometrial tissues from women with endometriosis and imply a role for resistin in endometriosis-associated pelvic inflammation.

 

 

Pain. 2017 Oct;158(10):1925-1937.

Visceral pain as a triggering factor for fibromyalgia symptoms in comorbid patients.

Costantini R1Affaitati GWesselmann UCzakanski PGiamberardino MA.

 

Abstract

Fibromyalgia syndrome (FMS) is a central sensitization syndrome; however, peripheral pain sources potentially exacerbate its symptoms of chronic diffuse musculoskeletal pain and hyperalgesia. This prospective study evaluated visceral pain as a possible triggering factor for FMS pain and hyperalgesia in comorbid patients. Women with (1) FMS + irritable bowel syndrome (IBS); (2) FMS + primary dysmenorrhea (Dys); (3) FMS + Dys secondary to endometriosis (Endo); (4) FMS + colon diverticulosis (Div) were compared with FMS-only women, for fibromyalgia pain (number and intensity of episodes and analgesic consumption) over comparable periods and for somatic hyperalgesia (electrical and pressure pain thresholds) in painful (tender points) and control areas (trapezius, deltoid, quadriceps muscles, and overlying subcutis and skin). In comorbid subgroups, FMS symptoms were also reassessed after treatment of the visceral condition or no treatment. All comorbid groups vs FMS-only had significantly higher FMS pain (number/intensity of episodes and analgesic consumption) and hyperalgesia in deep somatic tissues (subcutis and muscle) at all sites (0.05 < P < 0.0001). Visceral pain (number of IBS days, painful menstrual cycles, and abdominal pain episodes from diverticulitis) correlated directly with all parameters of FMS pain and inversely with muscle pain thresholds at all sites (0.03 < P < 0.0001). Fibromyalgia syndrome pain and hyperalgesia in all tissues and all sites significantly decreased in patients after visceral comorbidity treatment (dietary for 6 months [IBS], hormonal for 6 months [dysmenorrhea], laser [endometriosis], and surgery [diverticulosis]) (0.05 < P < 0.0001) vs no change in untreated patients. Visceral pain enhances FMS symptoms, probably augmenting the level of central sensitization typical of the syndrome. Systematic assessment and treatment of visceral pain comorbidities should be a part of FMS management strategy.

 

 

Reprod Sci. 2017 Jan 1:1933719117718276

Dysregulation of GdA Expression in Endometrium of Women With Endometriosis: Implication for Endometrial Receptivity.

Focarelli R1Luddi A2,3De Leo V2,3Capaldo A2,3Stendardi A2Pavone V1Benincasa L1Belmonte G2Petraglia F2,3Piomboni P2,3.

 

Abstract

Glycodelin-A (GdA) has been proposed to represent a potential biomarker of endometrial function, but little is known about its expression during the different phases of the menstrual cycle and under pathological conditions. In the light of its potential importance also in embryo implantation, we aimed to evaluate the expression profile of GdA as well as the presence of different glycosylated glycoforms and the immunolocalization in endometrial tissue from women with endometriosis and in women with proven fertility, at different times during the menstrual cycle. Our results showed that GdA is synthesized by endometrial epithelial and stromal cells, both in healthy endometrium and eutopic endometrium from women with endometriosis, with a profile including several glycosylated glycoforms, differentially expressed in each phase of the menstrual cycle. During the secretory phase, a significant increase in GdA protein expression, with a different glycoforms profile, was observed in endometriotic eutopic endometrium. Protein localization in eutopic endometrial tissue resulted significantly different in comparison with endometrium from women with proven fertility. This study indicate that GdA is a complex glycoprotein including up to 6 different glycoforms specifically expressed during the different phase of the menstrual cycle; in pathologic conditions such as endometriosis, the expression profile is altered possibly related to the impaired endometrial receptivity.

 

 

 

 

Reprod Sci. 2018 Jan;25(1):39-43.

Postoperative Levonorgestrel-Releasing Intrauterine System Insertion After Gonadotropin-Releasing Hormone Agonist Treatment for Preventing Endometriotic Cyst Recurrence: A Prospective Observational Study.

Kim MK1Chon SJ2Lee JH3,4Yun BH3,4Cho S4,5Choi YS3,4Lee BS3,4Seo SK3,4.

 

Abstract

OBJECTIVE:

The aim of this study was to evaluate the effectiveness of postoperative levonorgestrel-releasing intrauterine system (LNG-IUS) insertion after gonadotropin-releasing hormone agonist (GnRH-a) treatment for preventing endometriotic cyst recurrence.

STUDY DESIGN:

The LNG-IUS was applied to 28 women who had undergone surgery for endometriosis followed by 6 cycles of GnRH-a treatment. Clinical characteristics, endometriosis recurrence, and adverse effects were analyzed. Student t test was performed for analysis.

RESULTS:

Before surgery, 20 (71.4%) patients had dysmenorrhea, and the mean pain score (visual analog scale [VAS]) was 4.26. The numbers of women diagnosed with stage III endometriosis and stage IV endometriosiswere 15 (53.6%) and 13 (46.4%), respectively, according to the revised American Fertility Society scoring system. The mean cancer antigen 125 levels and VAS scores were significantly lower after treatment than before treatment (11.61 vs 75.66 U/mL, P < .0001 and 0.50 vs 4.26 U/mL, P < .0001, respectively). Of the 28 patients, 13 (46.4%) simultaneously had adenomyosis, and 2 (7.1%) underwent LNG-IUS removal because of unresolved vaginal bleeding and dysmenorrhea. Recurrence was noted in 2 (7.1%) women.

CONCLUSION:

Postoperative LNG-IUS insertion after GnRH-a treatment is an effective approach for preventing endometriotic cyst recurrence, especially in women who do not desire to conceive.

 

 

Best Pract Res Clin Obstet Gynaecol. 2017 Jul;42:100-113.

Genetics of gynaecological disorders.

Josifova DJ1.

 

Abstract

From genomic imbalances associated with developmental abnormalities of the female genital tract to the molecular mechanisms underpinning endometriosis and uterine leiomyomatosis, new technologies have allowed the exploration of the genetic contribution and mapping the molecular pathways underpinning common and rare gynaecological conditions. While some of these conditions have historically been considered sporadic, recent research has demonstrated their potentially heritable nature linked to single genes or copy number variants. The phenotypic variability including non-penetrance indicates their multifactorial, complex aetiology encompassing genetic, epigenetic and environmental influences. Although genetic tests are not routinely conducted in gynaecological practice, there is an increasing body of evidence suggesting that, in appropriate cases, molecular investigations such as array CGH analysis may be an important part of the diagnostic algorithm. The subtlety of clinical features, especially in the context of syndromic diagnoses, requires the practitioner to become familiar with those conditions and the approach to diagnostic investigations. This chapter combines the recent research output related to gynaecological disorders with a clinical genetics approach aiming to highlight the multisystem character of some of these conditions, their implications for management, reproductive risks and options, and the importance of genetic counselling.

 

 

Clin Genitourin Cancer. 2017 Dec;15(6):e1007-e1014.

Müllerian Adenosarcoma of the Urinary Bladder: Clinicopathologic and Immunohistochemical Features With Novel Genetic Aberrations.

Sanfrancesco J1Williamson SR2Kum JB1Zhang S1Wang M1Lopez-Beltran A3Montironi R4Gardner TA5Cheng L6.

 

Abstract

BACKGROUND:

Müllerian adenosarcoma is a biphasic neoplasm most commonly occurring in the uterus and less frequently of the ovary. It has been rarely described to occur in other sites such as peritoneum and liver.

PATIENTS AND METHODS:

In this study, we report the clinicopathologic, immunohistochemical and molecular features of a primary Müllerian adenosarcoma of the urinary bladder in a 62-year-old woman. To our knowledge, this is the first report of detailed pathologic characterization of Müllerian adenosarcoma primary to the urinary bladder in the literature.

RESULTS:

Light microscopy showed a biphasic epithelial and stromal tumor with benign-appearing glands surrounded by densely cellular endometrial-type stroma that is densely cellular with increased mitotic figures. The stroma surrounding the glands was more cellular than the intervening areas, which were more loose and edematous. Immunohistochemistry staining revealed positive staining for Pax-2/8 within the glands, for positive CD10 and WT-1 within the spindle cell stroma, and for estrogen and progesterone receptors in both. Staining for desmin, GATA3, p63, and human papillomavirus was negative. Molecular analyses identified mutations in protein kinase B E17K, fms related tyrosine kinase 3 D835N, KRAS proto-oncogene, GTPase G12D, and HRAS proto-oncogene, GTPase G12S. These novel molecular aberrations have yet to be reported in the medical literature. X chromosome inactivation analysis revealed a clonal pattern in the stromal component and a nonclonal pattern in the epithelial component. Currently, the patient is disease/recurrence-free after regular follow-up of approximately 84 months.

CONCLUSION:

This case represents, to our knowledge, the first reported diagnosis of Müllerian adenosarcoma arising in the urinary bladder with extensive clinicopathologic, immunohistochemical, and molecular analyses.

 

 

Reprod Sci. 2017 Jan 1:1933719117718271.

Lipoxin A4 Suppresses Estrogen-Induced Epithelial-Mesenchymal Transition via ALXR-Dependent Manner in Endometriosis.

Wu RF1,2,3Huang ZX2,3Ran J1Dai SJ1Lin DC1Ng TW1Chen QX2,3Chen QH1.

 

Abstract

OBJECTIVE:

Epithelial-mesenchymal transition (EMT) is essential for embryogenesis, fibrosis, and tumor metastasis. Aberrant EMT phenomenon has been reported in endometriotic tissues of patients with endometriosis (EM). In this study, we further investigated the molecular mechanism of which lipoxin A4 (LXA4) suppresses estrogen (E2)-induced EMT in EM.

STUDY DESIGN:

The EMT markers were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot in eutopic endometrial epithelial cells (EECs) or investigated by immunohistochemistry and qRT-PCR in endometriotic lesion of EM mice. The invasion and migration under different treatments were assessed by transwell assays with or without Matrigel. The messenger RNA (mRNA) and activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were determined by qRT-PCR and gelatin zymography, respectively. Luciferase reporter assay was used to measure the activity of zinc finger E-box binding homeobox 1(ZEB1) promoter. The level of E2 in endometriotic tissues was assessed by enzyme-linked immunosorbent assay.

RESULTS:

In eutopic EECs, stimulatory effects of E2 on EMT progress, migration, and invasion were all diminished by LXA4. Lipoxin A4 reduced E2-induced ZEB1 promoter activity. Lipoxin A4 also attenuated the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase induced by E2. Co-incubation with Boc-2 rather than DMF antagonized the influence of LXA4. Animal experiments showed that LXA4 inhibited the EMT progress, MMP expression, and proteinase activities of endometriotic lesion in an LXA4receptor (ALXR) manner, which suppressed the progression of EM. ZEB1 mRNA expression was upregulated and well correlated with E2 level in human endometrium.

CONCLUSION:

Lipoxin A4 suppresses E2-induced EMT via ALXR-dependent manner in eutopic EECs, which reveals a novel biological effect of LXA4 in EM.

 

 

Reprod Biomed Online. 2017 Nov;35(5):592-601.

Pathogenesis of adenomyosis: an update on molecular mechanisms.

Vannuccini S1Tosti C1Carmona F2Huang SJ3Chapron C4Guo SW5Petraglia F6.

 

Abstract

Adenomyosis is a uterine disorder becoming more commonly diagnosed in women of reproductive age because of diagnostic imaging advancements. The new epidemiological scenario and the clinical evidence of pelvic pain, abnormal uterine bleeding and infertility are changing the classic perspective of adenomyosis as a premenopausal disease. In the last decade, the evaluation of multiple molecular mediators has improved our knowledge of pathogenic mechanisms of adenomyosis, supporting that this is an independent disease from endometriosis. Although they share common genetic mutations and epigenetic changes in sex steroid hormone receptors and similar inflammatory mediators, an increasing number of recent studies have shown pathogenic pathways specific for adenomyosis. A PubMed search up to October 2016 summarizes the key mediators of pain, abnormal uterine bleeding and infertility in adenomyosis, including sex steroid hormone receptors, inflammatory molecules, extracellular matrix enzymes, growth factors and neuroangiogenic factors.

 

 

 

 

Urology. 2017 Oct;108:65-70.

Deep Infiltrating Endometriosis-Urinary Tract Involvement and Predictive Factors for Major Surgery.

Freire MJ1Dinis PJ2Medeiros R3Sousa L2Águas F3Figueiredo A4.

 

Abstract

OBJECTIVE:

To evaluate urinary tract involvement by deep infiltrating endometriosis as well as the surgical treatment and existence of predictive factors for major urologic surgery.

METHODS:

We conducted a retrospective analysis of 656 women submitted to surgery for endometriosis, of which 28 patients underwent minor or major surgery for deep infiltrating endometriosis involving the urinary tract, with a mean age of 38 ± 6.9 years (27-50) at diagnosis. Clinical data, surgeries performed, and complications were analyzed. Minor surgery was defined by endoscopic surgery or insertion of a percutaneous nephrostomy catheter, and major surgery included open or laparoscopic procedures.

RESULTS:

Endometriomas affected the ureter in 13 (46.4%), the bladder in 11 (39.3%), and both structures in 4 (14.3%) patients. Twelve (42.9%) patients had decreased renal function, and ureteral involvement was predictive of renal function loss (P = .034). Minor surgeries were performed in most women with isolated bladder involvement and in 12 (42.9%) patients with ureteral infiltration. Patients with ureteric involvement underwent major surgeries more often (n = 12 vs n = 3; P = .025) and had longer hospitalization (8.2 vs 3.1 days, P = .05). After a mean follow-up of 36.3 (1-102) months, there was no bladder involvement recurrence. The most common complication was ureteral stenosis (Clavien-Dindo grade IIIb) in 3 (10.7%) patients.

CONCLUSION:

Surgery is highly successful in most cases. Patients with ureteric involvement are more likely to lose kidney function, undergo major surgery, and have longer hospitalization.

 

 

J Minim Invasive Gynecol. 2017 Nov – Dec;24(7):1170-1176.

Initial Accuracy and Learning Curve of Transvaginal Ultrasound with Bowel Preparation for Deep Endometriosis in a United States Tertiary Care Center.

Young SW1Dahiya N2Patel MD2Abrao MS3Magrina JF2Temkit M2Kho RM4.

 

Abstract

STUDY OBJECTIVE:

To evaluate the diagnostic accuracy and learning curve of a sonographic mapping protocol for deep endometriosis (DE).

DESIGN:

Patients with pelvic pain at our institution underwent transvaginal ultrasound with bowel-preparation (TVUS-BP) performed by a single radiologist. Findings suspicious for DE were reported and correlated to surgical and histopathologic findings. The exam duration and number of cases required to achieve proficiency were calculated for positive, equivocal and negative findings.

DESIGN:

Classification: A retrospective cohort study, Canadian Task Force II-3.

SETTING:

United States tertiary referral center.

PATIENTS:

117 consecutive patients who presented to our gynecology clinic with complaints of significant noncyclic pelvic pain of at least 6 months’ duration, and/or clinical findings concerning for deep endometriosiswere referred for transvaginal ultrasound with bowel-preparation.

INTERVENTIONS:

Transvaginal ultrasound following bowel preparation; laparoscopic or robotic-assisted pelvic surgery.

MEASUREMENTS AND MAIN RESULTS:

Of 117 patients (median age 35, range 19-54) referred for TVUS-BP, 113 had completed exams. 57 of 113 patients underwent surgical exploration within one year and DE was identified surgically in 23. DE of the rectosigmoid colon and/or rectovaginal septum was detected with sensitivity of 94% (95% CI 70-100) and specificity of 100% (95% CI 91-100). DE of the retrocervical region and/or uterosacral ligaments was detected with sensitivity of 86% (95% CI 65-97) and specificity of 94% (95% CI 81-99). Proficiency, defined by flattening of the learning curve, was achieved after 70-75 scans. Initial exam duration was 42 minutes (+/- 4) but declined to 15 minutes (+/- 4) after proficiency was achieved. Cases showing equivocal or minimal disease demonstrated the greatest decline in exam duration.

CONCLUSION:

A newly applied TVUS-BP protocol for detection of pelvic DE was highly accurate and required a modest learning curve to achieve procedural proficiency in a United States (US) tertiary referral center where physicians interpret but typically do not perform TVUS exams. Overcoming diagnostic uncertainty regarding minimal or equivocal disease appeared to be an important factor in the initial learning curve. With adequate training, TVUS-BP may be adapted as a primary diagnostic tool for detecting pelvic DE.

 

 

Pilot Feasibility Stud. 2017 Jul 6;4:10.

Manual acupuncture plus usual care versus usual care alone in the treatment of endometriosis-related chronic pelvic pain: study protocol for a randomised controlled feasibility study.

Armour M1Smith CA1Schabrun S2Steiner GZ1Zhu X1Lawson K3Song J4.

 

Abstract

BACKGROUND:

Endometriosis is the most common cause of chronic pelvic pain worldwide. Non-surgical treatments are effective for only 30-50% of women and have a significant side effect burden that leads to high discontinuation rates. Surgery can be effective but is expensive and invasive, and symptoms tend to recur within 5 years. There is early evidence that acupuncture may be effective in treating endometriosis-related chronic pelvic pain, showing clinically significant analgesia. Both levels of inflammation and pain processing have been shown to be altered in women with chronic pelvic pain. Acupuncture has been shown to reduce inflammation and change central pain processing in other conditions, but research on women with endometriosis is currently lacking. The aim of this feasibility study is to provide data on recruitment rates, retention, appropriateness of outcome measures, minimal clinically important difference in numeric rated scales for pain and the potential effect of acupuncture on pain processing and markers of inflammation in endometriosis-related CPP.

METHODS:

We will include women aged 18-45 years with a diagnosis of endometriosis via laparoscopy in the past 5 years. A total of 30 participants will be recruited and randomly allocated in a 1:1 ratio to receive acupuncture or usual care. Women in the acupuncture group will receive two 45-min treatment sessions per week for 8 weeks (total of 16 sessions). Women in the usual care group will continue with their current treatment regimen. The primary feasibility outcomes are recruitment rates, retention rates and the safety and acceptability of the intervention; secondary patient-centred outcomes include a change in 0-10 daily pelvic pain ratings, the Endometriosis Health Profile 30 (EHP-30) and changes in conditioned pain modulation, resting and task-related EEG activity and inflammatory markers. Analyses will be performed blind to group allocation.

DISCUSSION:

This is a two-armed, assessor blind, randomised controlled feasibility trial. Data will be compared at baseline and trial completion 8 weeks later. Outcomes from this feasibility study will inform a larger, fully powered clinical trial should the treatment show trends for potential effectiveness.

 

 

 

Jpn J Radiol. 2017 Sep;35(9):546-554.

Comparison of transvaginal sonography and computed tomography-colonography with contrast media and urographic phase for diagnosing deep infiltrating endometriosis of the posterior compartment of the pelvis: a pilot study.

Zannoni L1Del Forno S2Coppola F3Papadopoulos D3Valerio D3Golfieri R3Caprara G4Paradisi R2Seracchioli R2.

 

Abstract

PURPOSE:

To compare the diagnostic accuracy of transvaginal sonography (TVS) and computed tomography-colonography with contrast media and urographic phase (CTCU) in the preoperative detection of deep infiltrating endometriosis (DIE).

MATERIALS AND METHODS:

Forty-seven patients with clinical suspicion of DIE underwent preoperative TVS and CTCU. Imaging data were compared with histopathologic analysis. Sensitivity, specificity, positive and negative predictive values and test accuracies of the two modalities were calculated.

RESULTS:

For diagnosing intestinal DIE, TVS and CTCU had a sensitivity of 98 and 71%, specificity of 33 and 50%, positive predictive value of 91 and 91%, negative predictive value of 67 and 20%, accuracy of 89 and 68%, respectively. For diagnosing ureteral DIE, TVS and CTCU had a sensitivity of 10 and 60%, specificity of 94.8 and 70.2% on the right; sensitivity of 28.5 and 57.1%, specificity of 96.3 and 76.9% on the left, respectively.

CONCLUSION:

TVS should be regarded as an accurate, radiation-free first-line diagnostic modality for patients with suspicion of posterior endometriosis. CTCU should be regarded as a complementary imaging modality, particularly for sigmoid or ureteral endometriosis.

 

 

 

Is the oocyte quality affected by endometriosis? A review of the literature.

Sanchez AM1Vanni VS2Bartiromo L2Papaleo E1Zilberberg E3Candiani M2,4Orvieto R3,5Viganò P6.

 

Abstract

Endometriosis is an estrogen-dependent chronic inflammatory condition that affects women in their reproductive period causing infertility and pelvic pain. The disease, especially at the ovarian site has been shown to have a detrimental impact on ovarian physiology. Indeed, sonographic and histologic data tend to support the idea that ovarian follicles of endometriosis patients are decreased in number and more atretic. Moreover, the local intrafollicular environment of patients affected is characterized by alterations of the granulosa cell compartment including reduced P450 aromatase expression and increased intracellular reactive oxygen species generation. However, no comprehensive evaluation of the literature addressing the effect of endometriosis on oocyte quality from both a clinical and a biological perspective has so far been conducted. Based on this systematic review of the literature, oocytes retrieved from women affected by endometriosis are more likely to fail in vitro maturation and to show altered morphology and lower cytoplasmic mitochondrial content compared to women with other causes of infertility. Results from meta-analyses addressing IVF outcomes in women affected would indicate that a reduction in the number of mature oocytes retrieved is associated with endometriosis while a reduction in fertilization rates is more likely to be associated with minimal/mild rather than with moderate/severe disease. However, evidence in this field is still far to be conclusive, especially with regards to the effects of different stages of the disease and to the impact of patients’ previous medical/surgical treatment(s).

 

 

Diagn Interv Radiol. 2017 Jul-Aug;23(4):272-281.

Shining light in a dark landscape: MRI evaluation of unusual localization of endometriosis.

Gui B1Valentini ALNinivaggi VMiccò MZecchi VGrimaldi PPCambi FGuido MBonomo L.

 

Abstract

Endometriosis is a disease distinguished by the presence of endometrial tissue outside the uterine cavity with intralesional recurrent bleeding and resulting fibrosis. The most common locations for endometriosis are the ovaries, pelvic peritoneum, uterosacral ligaments, and torus uterinus. Typical symptoms are secondary dysmenorrhea and cyclic or chronic pelvic pain. Unusual sites of endometriosis may be associated with specific symptoms depending on the localization. Atypical pelvic endometriosis localizations can occur in the cervix, vagina, round ligaments, ureter, and nerves. Moreover, rare extrapelvic endometriosis implants can be localized in the upper abdomen, subphrenic fold, or in the abdominal wall. Magnetic resonance imaging (MRI) represents a problem-solving tool among other imaging modalities. MRI is an advantageous technique, because of its multiplanarity, high contrast resolution, and lack of ionizing radiation. Our purpose is to remind the radiologists the possibility of atypical pelvic and extrapelvic endometriosis localizations and to illustrate the specific MRI findings. Endometriotic tissue with hemorrhagic content can be distinguished from adherences and fibrosis on MRI imaging. Radiologists should keep in mind these atypical localizations in patients with suspected endometriosis, in order to achieve the diagnosis and to help the clinicians in planning a correct and complete treatment strategy.

 

 

J Obstet Gynaecol Res. 2017 Oct;43(10):1563-1569.

Long non-coding RNA LINC00261 inhibits cell growth and migration in endometriosis.

Sha L1Huang L1Luo X2Bao J2Gao L2Pan Q1Guo M1Zheng F2Wang H2.

 

Abstract

AIM:

A previous study reported that LINC00261 is significantly downregulated in human ectopic endometrial tissues. The present study aimed to explore whether LINC00261 is functional in endometriosis cell proliferation, apoptosis and migration.

METHODS:

By transfecting human endometriosis cell line CRL-7566 with plasmids containing LINC00261, we successfully established the cell CRL-7566/LINC00261 with a high LINC00261 expression level. Cell-counting kit-8 and colony formation assays were conducted to evaluate the effect of LINC00261 on cell proliferation, and flow cytometry analysis and transwell migration assay were conducted to evaluate its effect on cell apoptosis and cell migration, respectively.

RESULTS:

Cell-counting kit-8 and colony formation assays both indicated that LINC00261 could inhibit cell proliferation in CRL-7566. Flow cytometry analysis confirmed that LINC00261 mediated inhibition of cell proliferation, which might be a consequence of inducting apoptosis. Furthermore, transwell migration assay indicated that LINC00261 could inhibit cell migration in endometriosis.

 

 

J Obstet Gynaecol Res. 2017 Oct;43(10):1550-1554.

Curative effect of 1.88-mg and 3.75-mg gonadotrophin-releasing hormone agonist on stage III-IV endometriosis: Randomized controlled study.

Tang H1Wu R1Li X1Zhou Y1Liu Z1Wang C1Chen Y2Zhang F3.

 

Abstract

AIM:

To compare the therapeutic effect of 1.88-mg and 3.75-mg gonadotrophin-releasing hormone agonist (GnRHa) in the treatment of stage III-IV endometriosis after laparoscopic surgery.

METHODS:

Fifty patients with stage III-IV endometriosis diagnosed on laparoscopy were randomized into two groups according to GnRHa dose. Sex hormone level, symptoms of estrogen deficiency and lumbar vertebrae bone density were compared and analyzed between the two groups.

RESULTS:

Bone density was decreased in both groups at 20 weeks after treatment, and the degree of bone density loss in the full-dose group (5.6%) was higher than in the half-dose group (1.2%; P < 0.05). Surgery combined with the 3.75-mg GnRHa or with the 1.88-mg GnRHa relieved the degree of dysmenorrhea, although one case of light dysmenorrhea occurred in each group, but there was no significant difference (P > 0.05) after resumption of menstruation. Both groups had symptoms of perimenopause at 8 weeks after treatment (P > 0.05), but change in Kupperman score with time differed between the groups. At 16, 20 weeks after treatment, the symptoms of perimenopause in the half-dose group were improved, and Kupperman score was lower than at 8 weeks after treatment. In the full-dose group, however, Kupperman score was higher than at 8 weeks after treatment and higher than in the half-dose group (P < 0.05). After treatment, follicle-stimulating hormone and luteinizing hormone both decreased in both groups (P < 0.05), but there was no difference between the two groups (P > 0.05). Estradiol (E2) in the full-dose group was significantly lower than in the half-dose group (P < 0.05).

CONCLUSION:

The 1.88-mg GnRHa treatment can be used in III-IV endometriosis patients after laparoscopic surgery, to reduce perimenopausal symptoms, significantly improve bone loss, and achieve a good clinical effect.

 

 

J Obstet Gynaecol Res. 2017 Oct;43(10):1555-1562.

Management of ureteral endometriosis with hydronephrosis: Experience from a tertiary medical center.

Huang JZ1Guo HL1Li JB1Chen SQ1.

 

Abstract

AIM:

We report the clinical characteristics and experience of the surgical management of ureteral endometriosisin our institution.

METHODS:

We retrospectively reviewed the data of patients with hydronephrosis resulting from ureteral endometriosis.

RESULTS:

Forty-six patients with different degrees of hydronephrosis were included in the study; 35% had urinary tract symptoms. Concomitant involvement of the ipsilateral ovary occurred in more than two-thirds of the patients. Four patients had nephrectomy, one of which involved ureterolysis because of hydronephrosis recurrence six months later.

CONCLUSIONS:

Hydronephrosis may be caused by uncommon reasons, such as ureteral endometriosis, which can even cause silent loss of renal function. Routine ultrasound scanning of the upper urinary tract for severe stages of endometriosis is very important in order to detect any potential ureteral lesions. Ureterolysis should be considered as the first surgical step, not only to avoid iatrogenic ureteral injuries but also to better evaluate ureter involvement for further procedures. To warrant tension-free and lesion-free anastomosis, it is wise to perform ureteroneocystostomy for long-term sound results.

 

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