Mol Med Rep. 2018 Mar 29. doi: 10.3892/mmr.2018.8823. [Epub ahead of print]

Zearalenone regulates endometrial stromal cell apoptosis and migration via the promotion of mitochondrial fission by activation of the JNK/Drp1 pathway.

Wang H¹, Zhao X², Ni C¹, Dai Y³, Guo Y¹.

Abstract

Increased endometrial stromal cell (ESC) survival and migration is responsible for the development and progression of endometriosis. However, little is known about the mechanisms underlying ESC survival and migration, and limited therapeutic strategies that are able to reverse these abnormalities are available. The present study investigated the effects of zearalenone (ZEA) on ESC survival and migration, particularly focusing on mitochondrial fission and the c‑Jun N‑terminal kinase (JNK)/dynamin‑related protein 1 (Drp1) pathway. The results revealed that ZEA induced ESC apoptosis in a dose‑dependent manner. Furthermore, ZEA treatment triggered excessive mitochondrial fission resulting in structural and functional mitochondrial damage, leading to the collapse of the mitochondrial membrane potential and subsequent leakage of cytochrome c into the cytoplasm. This triggered the mitochondrial pathway of apoptosis. Additionally, ZEA‑induced mitochondrial fission decreased ESC migration through F‑actin/G‑actin homeostasis dysregulation. ZEA also increased JNK phosphorylation and subsequently Drp1 phosphorylation at the serine 616 position, resulting in Drp1 activation. JNK/Drp1 pathway inhibition abolished the inhibitory effects of ZEA on ESC survival and migration. In summary, the present study demonstrated that ZEA reduced ESC survival and migration through the stimulation of mitochondrial fission by activation of the JNK/Drp1 pathway.

J Enzyme Inhib Med Chem. 2018 Dec;33(1):743-754.

Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives.

Niinivehmas S¹, Postila PA¹, Rauhamäki S¹, Manivannan E^1,2, Kortet S^1,3, Ahinko M¹, Huuskonen P⁴, Nyberg N⁴, Koskimies P⁵, Lätti S¹, Multamäki E¹, Juvonen RO⁴, Raunio H⁴, Pasanen M⁴, Huuskonen J³, Pentikäinen OT^1,6.

Abstract

A comprehensive set of 3-phenylcoumarin analogues with polar substituents was synthesised for blocking oestradiol synthesis by 17-β-hydroxysteroid dehydrogenase 1 (HSD1) in the latter part of the sulphatase pathway. Five analogues produced ≥62% HSD1 inhibition at 5 µM and, furthermore, three of them produced ≥68% inhibition at 1 µM. A docking-based structure-activity relationship analysis was done to determine the molecular basis of the inhibition and the cross-reactivity of the analogues was tested against oestrogen receptor, aromatase, cytochrome P450 1A2, and monoamine oxidases. Most of the analogues are only modestly active with 17-β-hydroxysteroid dehydrogenase 2 – a requirement for lowering effective oestradiol levels in vivo. Moreover, the analysis led to the synthesis and discovery of 3-imidazolecoumarin as a potent aromatase inhibitor. In short, coumarin core can be tailored with specific ring and polar moiety substitutions to block either the sulphatase pathway or the aromatase pathway for treating breast cancer and endometriosis.

Reprod Sci. 2018 Jan 1

LPAR2 and LPAR4 are the Main Receptors Responsible for LPA Actions in Ovarian Endometriotic Cysts.

Kowalczyk-Zieba I¹, Woclawek-Potocka I¹, Wasniewski T², Boruszewska D¹, Grycmacher K¹, Sinderewicz E¹, Staszkiewicz J¹, Wolczynski S^3,4.

Abstract

Endometriosis has been considered as an estrogen (E2)-dependent and progesterone (P4)-resistant disease. On the other hand, lysophosphatidic acid (LPA) has been suggested as a significant modulator of ovarian pathology, acting via both LPA levels and LPA receptor (LPAR) upregulation. Therefore, the objective of the present study was to evaluate LPA concentration as well as LPARs, autotaxin (ATX), and phospholipase A2 (PLA2) expression in ovarian endometriotic cysts and normal endometrium with correlation of the expression of E2 and P4 receptors in endometriotic cysts. The analyses were carried out using the tissues derived from 37 patients with ovarian endometriosis and 20 endometrial samples collected from women without endometriosis were used as a control. We found that ovarian endometriotic cysts are a site of LPA synthesis due to the presence of enzymes involved in LPA synthesis in the tissue. Additionally, when we compared endometriotic cysts versus normal endometrium, we were able to show overexpression of 3 from 6 examined LPARs and both enzymes responsible for LPA synthesis in endometriotic cysts. Finally, we found the correlations between LPARs, ATX, and PLA2 and the expression of E2 and P4 receptors in endometriotic cysts. Owing to the high LPAR2 and LPAR4 transcript and protein expression in endometriotic ovarian cysts and positive correlations of both these receptors with the PR-B and ERβ, respectively, those receptors seem to be the most promising predictors of the endometriotic cysts as well as the main receptors responsible for LPA action in the ovarian endometriosis.

Reprod Sci. 2018 Jan 1

The Hyaluronic Acid System is Intact in Menstrual Endometrial Cells in Women With and Without Endometriosis.

Knudtson JF¹, McLaughlin JE¹, Santos MT¹, Binkley PA¹, Tekmal RR¹, Schenken RS¹.

Abstract

OBJECTIVE:

To characterize the production and degradation of hyaluronic acid (HA) in menstrual endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs) in women with and without endometriosis. To identify the presence of CD44, the primary receptor of HA, in menstrual EECs and ESCs in women with and without endometriosis.

DESIGN:

In vitro study.

SETTING:

Academic center.

PATIENT(S):

Deidentified patient samples from women with and without endometriosis.

INTERVENTIONS:

EECs and ESCs were isolated from menstrual endometrial biopsies performed on women with (N = 9) and without (N = 11) endometriosis confirmed by laparoscopy.

MAIN OUTCOME MEASURE:

Real-time polymerase chain reaction, Western blot, and immunohistochemistry were used to assess hyaluronic acid synthase (HAS) isoforms 1, 2, and 3; hyaluronidase (HYAL) isoforms 1 and 2; and standard CD44. Student t test was used to analyze the results.

RESULTS:

There was no significant difference in messenger RNA (mRNA) or protein expression of HAS2, HAS3, HYAL1, or HYAL2 in EECs or ESCs from women with or without endometriosis. HAS1 mRNA was variably detected, whereas HAS1 protein was similarly expressed in EECs and ESCs from women with and without endometriosis. Standard CD44 was expressed in both cell types, and expression did not differ in cells from women with or without endometriosis.

CONCLUSIONS:

The HA system is expressed in eutopic menstrual ESCs and EECs from women with and without endometriosis. There are no differences in expression in HA production or degradation enzymes in EECs or ESCs from women with and without endometriosis. Standard CD44 expression does not differ in eutopic menstrual endometrial cells from women with and without endometriosis.

Gene. 2018 Apr 3.

Identification of small-molecule ligands that bind to MiR-21 as potential therapeutics for endometriosis by screening ZINC database and in-vitro assays.

Liu S¹, Yang Y², Li W³, Tian X³, Cui H³, Zhang Q³.

Abstract

MicroRNA-21 (miR-21) is an important regulator of cell signaling pathways involved in the pathogenesis of endometriosis. Here, we attempted to discover new ligands of miR-21 pre-element by carrying out stepwise high-throughput virtual screening against a chemical library consisting of over 4 million lead-like compounds. In the procedure, a synthetic strategy that integrated empirical exclusion, molecular docking, druglikeness evaluation, consensus scoring and manual culling was employed to computationally identify seven promising hits from the large compound library, of which four were determined to have moderate or high affinity for miR-21 pre-element (K_D range between 3.7 and 109 μM). We also evaluated the putative binding site and predicted interaction mode of pre-element with its identified compound ligands by inversion mutation of the wild-type pre-element to mutant [U11A/A20U], and explored the sequence-specific recognition in pre-element-ligand interactions by generating a background of numerous random RNA decoys. It was revealed that most of identified pre-element binders are positively charged to meet the electrostatic complementarity with the negative electrostatic potential surface of RNA molecule, and the compound selectivity seems related partially to their affinity.

Am J Health Syst Pharm. 2018 Apr 15;75(8):532-535.

Probable fidaxomicin-induced pancytopenia.

Axtell S¹, Shokoya A², Yocum C².

Abstract

PURPOSE:

A case of pancytopenia in a patient receiving treatment with fidaxomicin for Clostridium difficile infection (CDI) is described.

SUMMARY:

A 33-year-old Caucasian woman was admitted to the hospital with a chief complaint of loose stools occurring approximately 7 times a day; she also reported fever, nausea, diffuse abdominal pain, and fatigue. The patient had a history of recurrent CDI, recurrent urinary tract infections, nephrolithiasis, chronic hepatitis C, and endometriosis. Her previous therapies for CDI included metronidazole, vancomycin, rifaximin, and fecal microbiota transplantation. On admission, she had a platelet count of 172,000 platelets/mm³, hemoglobin concentration of 11.1 g/dL, and white blood cell (WBC) count of 3,100 cells/mm³. Within 24 hours of the first dose of fidaxomicin and before the second dose, the patient’s platelet count fell to 156,000 platelets/mm³, her hemoglobin concentration decreased to 9.9 g/dL, and her WBC count fell to 2,600 cells/mm³. Values for all 3 tests continued to decrease during the first few days of fidaxomicin therapy. One dose of filgrastim 300 μg was administered subcutaneously on day 6 in response to the pancytopenia, after which the platelet, hemoglobin, and WBC values stabilized for a day and then generally declined. Platelet, hemoglobin, and WBC values returned to normal within 3 days of the patient’s last dose of fidaxomicin. Use of the Naranjo et al. adverse drug reaction probability scale indicated a probable association (score of 6) between fidaxomicin and the patient’s pancytopenia.

CONCLUSION:

A 33-year-old woman developed pancytopenia during a course of fidaxomicin therapy for CDI. Platelet, hemoglobin, and WBC values returned to normal within 3 days of the final fidaxomicin dose.

Reprod Biomed Online. 2018 Mar 27.

Prediction of Endometriosis Fertility Index in patients with endometriosis-associated infertility after laparoscopic treatment.

Zhang X¹, Liu D¹, Huang W², Wang Q¹, Feng X¹, Tan J¹.

Abstract

The effect of endometriosis on fecundity is unclear. Although surgery plays a vital role in the treatment of related infertility, pregnancy outcomes after laparoscopy are poorly correlated with the currently used staging system. To address this, the Endometriosis Fertility Index (EFI) was developed. This retrospective study was designed to assess the predictive value of the EFI for patients with endometriosis-associated infertility. A total of 1325 patients with endometriosis-associated infertility were eligible for inclusion, 1097 of whom were successfully interviewed and 228 lost to follow-up (17.21%). Cumulative pregnancy incidence (CPI) according to EFI scores were calculated by life table and by Kaplan-Meier survival curve analyses. The log-rank test was used to evaluate difference between the EFI groups. Receiver operating characteristic curves were plotted to obtain the optimal cut-off point for pregnancy prediction. A total of 505 (46.03%) patients conceived naturally. The difference in CPI among EFI scores 10, 7-9, 4-6, and 2-3 was statistically significant (P < 0.001) and increased with increasing EFI score. The optimal cut-off point was 7.5: sensitivity (68.51%); specificity (52.20%). This retrospective study indicates the value of the EFI score for predicting spontaneous pregnancy in women treated by laparoscopy for endometriosis-associated infertility.

J Midlife Health. 2018 Jan-Mar;9(1):44-46.

Squamous Cell Carcinoma Arising in Mature Teratoma of the Ovary Masquerading as Abdominal Tuberculosis.

Indulkar ST¹, Khare MS¹, Shah VB¹, Khade AL¹.

Abstract

Pure squamous cell carcinoma (SCC) of the ovary is rare. SCC can arise in a mature teratoma (MT), ovarian endometriosis or in a Brenner tumor. SCC is the most common malignant transformation arising in MT and comprises 80% of all cases. Such neoplastic transformations are extremely difficult either to predict or detect early. The mechanism of malignant transformation has not been completely understood. Due to the rarity and the aggressive course, diagnosis and treatment constitute a big challenge. We report a case of SCC arising in MT presenting with a huge abdominopelvic mass and abundant peritoneal collections clinically masquerading as abdominal tuberculosis. A review of literature with special emphasis on prognosis and treatment modalities is also presented.

Appl Immunohistochem Mol Morphol. 2018 Apr 7.

Human Endometriosis Tissue Microarray Reveals Site-specific Expression of Estrogen Receptors, Progesterone Receptor, and Ki67.

Colón-Caraballo M¹, García M², Mendoza A^3,4, Flores I^1,5.

Abstract

Most available therapies for endometriosis are hormone-based and generally broadly used without taking into consideration the ovarian hormone receptor expression status. This contrasts strikingly with the standard of care for other hormone-based conditions such as breast cancer. We therefore aimed to characterize the expression of ovarian steroid hormone receptors for estrogen alpha (ESR1), estrogen beta (ESR2), and progesterone (PGR) in different types of endometriotic lesions and eutopic endometrium from women with endometriosis and controls using a tissue microarray (TMA). Nuclear expression levels of the receptors were analyzed by tissue (ie, ectopic vs. eutopic endometrium) and cell type (ie, glands vs. stroma). Ovarian lesions showed the lowest expression of ESR1 and PGR, and the highest expression of ESR2, whereas the fallopian tube lesions showed high expression of the 3 receptors. Differences among endometria included lower expression of ESR1 and higher expression of ESR2 in stroma of proliferative endometrium from patients versus patients, and a trend towards loss of PGR nuclear positivity in proliferative endometrium from patients. The largest ESR2:ESR1 ratios were observed in ovarian lesions and secretory endometrium. The highest proportion of samples with >10% Ki67 positive nuclei was in glands of fallopian tube (54%) and extrapelvic lesions (75%); 60% of glands of secretory endometrium from patients had >10% Ki67 positivity compared with only 15% in controls. Our results provide a better understanding of endometriosis heterogeneity by revealing lesion type-specific differences and case-by-case variability in the expression of ovarian hormone receptors. This knowledge could potentially predict individual responses to hormone therapies, and set the basis for the application of personalized medicine approaches for women with endometriosis.

Eur Rev Med Pharmacol Sci. 2018 Mar;22(6):1554-1568.

Effect of FGF2 on the activity of SPRYs/DUSP6/ERK signaling pathway in endometrial glandular epithelial cells of endometriosis.

Yu XY¹, Wang XT, Chu YL, Qu HM, Liu J, Zhang YH, Li MJ.

Abstract

OBJECTIVE:

We aimed at exploring the positive feedback loop in eutopic and ectopic endometrial glandular epithelial cells (EuECs and EECs) in endometriosis.

MATERIALS AND METHODS:

Normal epithelial cells (NECs), EuECs and EECs were treated with fibroblast growth factor (FGF)2, FGF2 neutralizing antibody, mitogen-activated protein kinases (MAPKs) inhibitors U0126 and PD98059. FGF2 protein level was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of FGF2, FGF receptor 1 (FGFR1), extracellular signal-regulated kinase (ERK)1/2/pERK1/2 and Sproutys (SPRYs) (Sprouty1, Sprouty2, Sprouty4) and dual specificity phosphatase 6 (DUSP6) were detected by Western blot. The mRNA levels of FGF2, FGFR1 (FGF receptor 1), SPRYs (Sprouty1, Sprouty2, Sprouty4) and DUSP6 mRNA were detected by RT-PCR.

RESULTS:

Among treatment groups, the content of FGF2 in EuECs and EECs was significantly higher than that in NECs (p < 0.05). The mRNA and protein levels of FGF2, FGFR1, SPRYs (Sprouty1, Sprouty2, Sprouty4) and DUSP6 in EuECs and EECs were increased after adding FGF2 (p < 0.05), but decreased after adding FGF2 neutralizing antibody, no significant change was found in NECs (p > 0.05). The inhibitory effect of PD9805 on NECs was not significantly different from that of U0126 (p > 0.05); however, the inhibitory effects of PD9805 on EuECs and EECs were significantly lower than those of U0126 (p< 0.05).

CONCLUSIONS:

The positive feedback loop existed in EuECs and EECs, but maybe not in NECs. The results may provide the guideline to treat endometriosis patients.

PLoS One. 2018 Apr 9;13(4):e0194800.

The deferred embryo transfer strategy improves cumulative pregnancy rates in endometriosis-related infertility: A retrospective matched cohort study.

Bourdon M^1,2, Santulli P^1,2,3, Maignien C¹, Gayet V¹, Pocate-Cheriet K⁴, Marcellin L^1,2,3, Chapron C^1,2,3.

Abstract

BACKGROUND:

Controlled ovarian stimulation in assisted reproduction technology (ART) may alters endometrial receptivity by an advancement of endometrial development. Recently, technical improvements in vitrification make deferred frozen-thawed embryo transfer (Def-ET) a feasible alternative to fresh embryo transfer (ET). In endometriosis-related infertility the eutopic endometrium is abnormal and its functional alterations are seen as likely to alter the quality of endometrial receptivity. One question in the endometriosis ART-management is to know whether Def-ET could restore optimal receptivity in endometriosis-affected women leading to increase in pregnancy rates.

OBJECTIVE:

To compare cumulative ART-outcomes between fresh versus Def-ET in endometriosis-infertile women.

MATERIALS AND METHODS:

This matched cohort study compared def-ET strategy to fresh ET strategy between 01/10/2012 and 31/12/2014. One hundred and thirty-five endometriosis-affected women with a scheduled def-ET cycle and 424 endometriosis-affected women with a scheduled fresh ET cycle were eligible for matching. Matching criteria were: age, number of prior ART cycles, and endometriosis phenotype. Statistical analyses were conducted using univariable and multivariable logistic regression models.

RESULTS:

135 in the fresh ET group and 135 in the def-ET group were included in the analysis. The cumulative clinical pregnancy rate was significantly increased in the def-ET group compared to the fresh ET group [58 (43%) vs. 40 (29.6%), p = 0.047]. The cumulative ongoing pregnancy rate was 34.8% (n = 47) and 17.8% (n = 24) respectively in the Def-ET and the fresh-ET groups (p = 0.005). After multivariable conditional logistic regression analysis, Def-ET was associated with a significant increase in the cumulative ongoing pregnancy rate as compared to fresh ET (OR = 1.76, CI95% 1.06-2.92, p = 0.028).

CONCLUSION:

Def-ET in endometriosis-affected women was associated with significantly higher cumulative ongoing pregnancy rates. Our preliminary results suggest that Def-ET for endometriosis-affected women is an attractive option that could increase their ART success rates. Future studies, with a randomized design, should be conducted to further confirm those results.

Am J Pathol. 2018 Apr 6.

CD147 induces epithelial-to-mesenchymal transition by disassembling CAS/E-cadherin/β-catenin complex in human endometriosis.

Wang C¹, Zhang J¹, Fok KL¹, Tsang LL¹, Ye M², Liu J², Li F², Zhao AZ², Chan HC³, Chen H⁴.

Abstract

Epithelial-to-mesenchymal transition (EMT) is postulated to be a prerequisite for the establishment of endometriosis (EMS), a common reproductive disorder in women. Our previous studies have demonstrated the elevated expression of transmembrane glycoprotein CD147 and its pro-survival effect on abnormal cells in endometriosis. Intriguingly, CD147 is known to promote EMT in cancers. However, the involvement of CD147 in EMT during the establishment of endometriosis remains incompletely understood. Here, we showed that CD147 promotes EMT in human endometrial adenocarcinoma cell line Ishikawa (ISK). We identified a novel CD147-interacting partner, cellular apoptosis susceptibility protein (CAS), which stabilized the interaction between E-cadherin (E-cad) and β-catenin (β-cat) by forming CAS/E-cad/β-cat complex. Down-regulation of CAS led to the release and nuclear translocation of β-cat from E-cad, resulting in the overexpression of EMT-promoting gene SNAIL. Interestingly, overexpression of CD147 impaired the interaction between CAS and E-cad and triggered the release of β-cat from CAS/E-cad/β-cat complex, which in turn led to EMT. Furthermore, CAS was down-regulated in EMS with elevated levels of CD147 and nuclear β-cat. These findings suggest a previously undefined role of CAS in regulating EMT and reveal the involvement of a CD147-induced EMT signaling pathway in pathogenic progression of EMS.

Orv Hetil. 2018 Apr;159(15):603-609.

Investigation and treatment of prefibrotic/early primary myelofibrosis. A case study.

Magyari F¹, Bedekovics J², Décsy J³, Ilonczai P^4,5, Illés Á¹, Simon Z¹.

Abstract

Moderate thrombocytosis can accompany several diseases (bleeding, inflammation, iron deficiency, or autoimmune diseases), but hematologic examination is strongly recommended in a patient with persistent platelet count above 450 G/L unless reactive origin can be confirmed. The 47-year-old woman’s medical history included hypertonia, asthma bronchiale, and endometriosis. In March 2015, she underwent laboratory examination due to weight loss and lack of appetite. Her results showed elevated thrombocyte count (617 G/L), but no iron deficiency. She presented in our clinic on 07. 04. 2015 with acute pain below her left hypochondrial region, but simple imaging examinations showed no difference to explain it. Abdominal CT revealed a 4.5 cm thrombus which protruded into the left renal artery, blocking it. We started APTI- (activated partial thromboplastin time) monitored continuous intravenous treatment with unfractionated heparin. The JAK2V617F mutation analysis came back positive. Subsequent bone marrow examination revealed prefibrotic/early stage myelofibrosis, prompting treatment with hydroxyurea. The applied treatments led to the disappearance of the patient’s symptoms accompanied by the gradual normalisation of the thrombocyte count. Moderate thrombocytosis is often secondary, but if it persists and is accompanied by mainly thromboembolic events, the risk of diseases of the haematopoietic system, primarily Philadelphia chromosome negative chronic myeloproliferative disease should also be considered. Clinically, essential thrombocythaemia and the prefibrotic/early stage of myelofibrosis can be very similar. Differential diagnosis is only possible through the histological examination of the bone marrow, which becomes indispensible due to the difference in prognosis and treatment options. Orv Hetil. 2018; 159(15): 603-609.

Comp Med. 2019 Mar 1;68(2):177-181.

Repair of a Large Ventral Hernia in a Rhesus Macaque (Macaca mulatta) by Using an Abdominal Component Separation Technique.

Kempton SJ¹, Israel JS², Capuano Iii S³, Poore SO².

Abstract

Here we present a 32-y-old rhesus macaque (Macaca mulatta) with a large recurrent ventral incisional hernia. The initial surgery included midline celiotomy for treatment of endometriosis, in which the animal developed a hernia that was repaired with interposition of mesh. Hernia recurrence at 1 y resulted in a defect measuring 7 × 13 cm, with loss of abdominal domain. Skin breakdown was noted with areas of exposed mesh through the skin with associated acute on chronic infection. Clinically, the animal was lethargic, not eating, and failing to thrive. The present surgical treatment included midline celiotomy, removal of mesh, and attempted primary fascial closure. Due to the large defect and high tension, the fascia could not be closed. To facilitate closure, abdominal component separation technique was used and consisted of skin and subcutaneous dissection, external oblique muscle release, and dissection between the external and internal oblique musculature. This technique allowed for primary fascial closure and resection of excess diseased skin. A piece of polypropylene mesh was placed in a sublay fashion to reinforce the primary fascial closure. The animal tolerated the procedure well and has demonstrated steady weight gain, with no recurrence at 12 mo. Large ventral abdominal hernia defects in after surgery or trauma in NHP can present reconstructive challenges to veterinary surgeons. Failure to achieve a dynamic, low-tension closure can result in hernia recurrence, necessitating additional operations. Abdominal component separation is not commonly used in veterinary surgery and may be a helpful tool in cases of difficult abdominal reconstructions.

BMJ Open. 2018 Apr 9;8(4):e018924.

Laparoscopic excision of deep rectovaginal endometriosis in BSGE endometriosis centres: a multicentre prospective cohort study.

Byrne D¹, Curnow T², Smith P³, Cutner A⁴, Saridogan E⁴, Clark TJ⁵; BSGE Endometriosis Centres.

Abstract

OBJECTIVE:

To estimate the effectiveness and safety of laparoscopic surgical excision of rectovaginal endometriosis.

DESIGN:

A multicentre, prospective cohort study.

SETTING:

51 hospitals accredited as specialist endometriosis centres.

PARTICIPANTS:

5162 women of reproductive age with rectovaginal endometriosis of which 4721 women had planned laparoscopic excision.

INTERVENTIONS:

Laparoscopic surgical excision of rectovaginal endometriosis requiring dissection of the pararectal space.

MAIN OUTCOME MEASURES:

Standardised symptom questionnaires enquiring about chronic pelvic pain, bladder and bowel symptoms, analgesia use and quality of life (EuroQol) completed prior to surgery and at 6, 12 and 24 months postoperatively. Serious perioperative and postoperative complications including major haemorrhage, infection and visceral injury were recorded.

RESULTS:

At 6 months postsurgery, there were significant reductions in premenstrual, menstrual and non-cyclical pelvic pain, deep dyspareunia, dyschezia, low back pain and bladder pain. In addition, there were significant reductions in voiding difficulty, bowel frequency, urgency, incomplete emptying, constipation and passing blood. These reductions were maintained at 2 years, with the exception of voiding difficulty. Global quality of life significantly improved from a median pretreatment score of 55/100 to 80/100 at 6 months. There was a significant improvement in quality of life in all measured domains and in quality-adjusted life years. These improvements were sustained at 2 years. All analgesia use was reduced and, in particular, opiate use fell from 28.1% prior to surgery to 16.1% at 6 months. The overall incidence of complications was 6.8% (321/4721). Gastrointestinal complications (enterotomy, anastomotic leak or fistula) occurred in 52 (1.1%) operations and of the urinary tract (ureteric/bladder injury or leak) in 49 (1.0%) procedures.

CONCLUSION:

Laparoscopic surgical excision of rectovaginal endometriosis appears to be effective in treating pelvic pain and bowel symptoms and improving health-related quality of life and has a low rate of major complications when performed in specialist centres.

Oncotarget. 2018 Feb 22;9(20):15266-15274.

PIK3CA and KRAS mutations in cell free circulating DNA are useful markers for monitoring ovarian clear cell carcinoma.

Morikawa A^1,2, Hayashi T¹, Shimizu N¹, Kobayashi M¹, Taniue K¹, Takahashi A¹, Tachibana K¹, Saito M², Kawabata A^1,2, Iida Y², Ueda K², Saito M², Yanaihara N², Tanabe H³, Yamada K², Takano H³, Nureki O⁴, Okamoto A², Akiyama T¹.

Abstract

Ovarian clear cell carcinoma (OCCC) exhibits distinct phenotypes, such as resistance to chemotherapy, poor prognosis and an association with endometriosis. Biomarkers and imaging techniques currently in use are not sufficient for reliable diagnosis of this tumor or prediction of therapeutic response. It has recently been reported that analysis of somatic mutations in cell-free circulating DNA (cfDNA) released from tumor tissues can be useful for tumor diagnosis. In the present study, we attempted to detect mutations in PIK3CA and KRAS in cfDNA from OCCC patients using droplet digital PCR (ddPCR). Here we show that we were able to specifically detect PIK3CA-H1047R and KRAS-G12D in cfDNA from OCCC patients and monitor their response to therapy. Furthermore, we found that by cleaving wild-type PIK3CA using the CRISPR/Cas9 system, we were able to improve the sensitivity of the ddPCR method and detect cfDNA harboring PIK3CA-H1047R. Our results suggest that detection of mutations in cfDNA by ddPCR would be useful for the diagnosis of OCCC, and for predicting its recurrence.

J Endocrinol. 2018 Apr 10. pii: JOE-17-0700.

Bufalin suppresses endometriosis progression by inducing pyroptosis and apoptosis.

Cho YJ¹, Lee JE², Park MJ³, O’Malley BW⁴, Han SJ⁵.

Abstract

The steroid receptor coactivator (SRC)-1 isoform/estrogen receptor (ER)-β axis has an essential role in endometriosis progression. In this context, therefore, bufalin was employed as a ‘tool compound’ to evaluate inhibitors of SRC in alternative endometriosis treatment. Bufalin effectively suppressed the growth of primary human endometrial stroma cells isolated from endometriosis patients compared to women without endometriosis and immortalized human endometrial epithelial and stromal cells expressing the SRC-1 isoform compared to their parental cells in vitro. In vivo, compared to the vehicle, bufalin treatment significantly suppressed the growth of endometriotic lesions in mice with surgically induced endometriosis because bufalin disrupted the functional axis of SRC-1 isoform/ERβ by increasing SRC-1 isoform protein stability, hyperactivating the transcriptional activity of the SRC-1 isoform, and degrading the ERβ protein by proteasome 26S subunit, non-ATPase 2 in endometriotic lesions. Bufalin treatment elevated the apoptosis signaling in epithelial cells of endometriotic lesions. In stromal cells of endometriotic lesions, bufalin treatment increased the levels of pyroptosis markers (caspase 1 and the active form of interleukin 1β) and reduced proliferation. In addition, bufalin treatment increased the expression levels of endoplasmic reticulum (ER)-stress markers (PKR-like ER kinase, protein disulfide isomerase and binding immunoglobulin) in endometriotic lesions. Collectively, the bufalin-induced disruption of the SRC-1 isoform/ERβ axis might dysregulate apoptosis, pyroptosis and ER-stress signaling in endometriotic lesions, causing the suppression of endometriosis. Therefore, future generations of SRC-modulators could be employed as an alternative medical approach for endometriosis treatment.

Reproduction. 2018 Apr 10. pii: REP-17-0566.

The Impact of Infertility Diagnosis on Embryo-Endometrial Dialogue.

Parks JC¹, McCallie BR², Patton AL³, Al-Safi ZA⁴, Polotsky A⁵, Griffin D⁶, Schoolcraft WB⁷, Katz-Jaffe MG⁸.

Abstract

Initial stages of implantation involve bi-directional molecular cross-talk between the blastocyst and endometrium. This study investigated an association between infertility etiologies, specifically advanced maternal age (AMA) and endometriosis, on the embryo-endometrial molecular dialogue prior to implantation. Co-culture experiments were performed with endometrial epithelial cells (EECs) and cryopreserved day 5 blastocysts (n=41 ≥ Grade 3BB) donated from patients presenting with AMA or endometriosis, compared to fertile donor oocyte controls. Extracellular vesicles isolated from co-culture supernatant were analyzed for miRNA expression and revealed significant alterations correlating to AMA or endometriosis. Specifically, AMA resulted in 16 miRNAs with increased expression (P ≤ 0.05) and strong evidence for negative regulation towards 206 target genes. VEGFA, a known activator of cell adhesion, displayed decreased expression (P ≤ 0.05), validating negative regulation by 4 of these increased miRNAs: miR-126; 150; 29a; 29b (P ≤ 0.05). In endometriosis patients, a total of 10 significantly altered miRNAs displayed increased expression compared to controls (miR-7b; 9; 24; 34b; 106a; 191; 200b; 200c; 342-3p; 484) (P ≤ 0.05), targeting 1014 strong evidence-based genes. Three target genes of miR-106a (CDKN1A, E2F1 and RUNX1) were independently validated. Functional annotation analysis of miRNA target genes revealed enriched pathways for both infertility etiologies, including disrupted cell cycle regulation and proliferation (P ≤ 0.05). These extracellular vesicle-bound secreted miRNAs are key transcriptional regulators in embryo-endometrial dialogue and may be prospective biomarkers of implantation success. One of the limitations of this study is that it was a stimulated, in-vitro model and therefore may not accurately reflect the in-vivo environment.

Evid Based Complement Alternat Med. 2018 Jan 30;2018

Shaofu Zhuyu Decoction Regresses Endometriotic Lesions in a Rat Model.

Zhu G^1,2, Jiang C¹, Yan X¹, Zhao S¹, Xu D¹, Cao Y¹.

Abstract

The current therapies for endometriosis are restricted by various side effects and treatment outcome has been less than satisfactory. Shaofu Zhuyu Decoction (SZD), a classic traditional Chinese medicinal (TCM) prescription for dysmenorrhea, has been widely used in clinical practice by TCM doctors to relieve symptoms of endometriosis. The present study aimed to investigate the effects of SZD on a rat model of endometriosis. Forty-eight female Sprague-Dawley rats with regular estrous cycles went through autotransplantation operation to establish endometriosis model. Then 38 rats with successful ectopic implants were randomized into two groups: vehicle- and SZD-treated groups. The latter were administered SZD through oral gavage for 4 weeks. By the end of the treatment period, the volume of the endometriotic lesions was measured, the histopathological properties of the ectopic endometrium were evaluated, and levels of proliferating cell nuclear antigen (PCNA), CD34, and hypoxia inducible factor- (HIF-) 1α in the ectopic endometrium were detected with immunohistochemistry. Furthermore, apoptosis was assessed using the terminal deoxynucleotidyl transferase (TdT) deoxyuridine 5′-triphosphate (dUTP) nick-end labeling (TUNEL) assay. In this study, SZD significantly reduced the size of ectopic lesions in rats with endometriosis, inhibited cell proliferation, increased cell apoptosis, and reduced microvessel density and HIF-1α expression. It suggested that SZD could be an effective therapy for the treatment and prevention of endometriosis recurrence.

Which Ultrasound-Guided Sciatic Nerve Block Strategy Works Faster? Prebifurcation or Separate Tibial-Peroneal Nerve Block? A Randomized Clinical Trial.

Faiz SHR¹, Imani F², Rahimzadeh P³, Alebouyeh MR⁴, Entezary SR⁵, Shafeinia A⁶.

Abstract

BACKGROUND:

Peripheral nerve block is an accepted method in lower limb surgeries regarding its convenience and good tolerance by the patients. Quick performance and fast sensory and motor block are highly demanded in this method. The aim of the present study was to compare 2 different methods of sciatic and tibial-peroneal nerve block in lower limb surgeries in terms of block onset.

METHODS:

In this clinical trial, 52 candidates for elective lower limb surgery were randomly divided into 2 groups: sciatic nerve block before bifurcation (SG; n = 27) and separate tibial-peroneal nerve block (TPG; n = 25) under ultrasound plus nerve stimulator guidance. The mean duration of block performance, as well as complete sensory and motor block, was recorded and compared between the groups.

RESULTS:

The mean duration of complete sensory block in the SG and TPG groups was 35.4 ± 4.1 and 24.9 ± 4.2 minutes, respectively, which was significantly lower in the TPG group (P = 0.001). The mean duration of complete motor block in the SG and TPG groups was 63.3 ± 4.4 and 48.4 ± 4.6 minutes, respectively, which was significantly lower in the TPG group (P = 0.001). No nerve injuries, paresthesia, or other possible side effects were reported in patients.

CONCLUSIONS:

According to the present study, it seems that TPG shows a faster sensory and motor block than SG.

Heavy menstrual bleeding.

Editors

National Collaborating Centre for Women’s and Children’s Health (UK).

Excerpt

Heavy menstrual bleeding (HMB) has an adverse effect on the quality of life of many women. It is not a problem associated with significant mortality. Many women seek help from their general practitioners and it is a common reason for referral into secondary care. In order for women to be treated successfully, it is essential that the underlying problem is understood by both the patient and the healthcare professional. This guideline provides background information as well as covering epidemiology, physiology, investigation and, ultimately, treatment. The aim is to consider the evidence and review it, taking into account both the woman’s and the healthcare professional’s viewpoints and interests. This is not always easy but it is anticipated that the beneficial decision with their doctors. Once they have read the guideline, they will know what questions to ask and what the options available to them are. Constructive dialogue should allow patients to be able to trust the advice given by their practitioner as they will be confident that they have the latest information and will be able to use it to inform this decision-making process. Clinical guidelines have been defined as systematically developed statements which assist clinicians and patients in making decisions about appropriate treatment for specific conditions. This guideline has been developed with the aim of providing guidance on HMB. The effectiveness of the various treatments as well as their risks and benefits are discussed in relation to their use in the treatment of HMB but the discussion cannot be extrapolated to the use of particular treatments to relieve other symptoms, such as hysterectomy for cancer or endometriosis. The implications of each treatment in relation to fertility are also clearly stated so that no woman will undergo treatment that renders her infertile unless this is her specific wish.

Expert Opin Pharmacother. 2018 Apr 11:1-10.

Levonorgestrel-releasing intra-uterine systems as female contraceptives.

Grandi G¹, Farulla A¹, Sileo FG¹, Facchinetti F¹.

Abstract

The availability and use of long-acting reversible contraceptives (LARCs), such as levonorgestrel intrauterine systems (LNG-IUSs), have increased in recent times. Areas covered: The authors provide a narrative review of the LNG-IUSs currently available worldwide as female contraceptives (LNG-IUS 13.5, 19.5 and 52 mg). Specific features of the devices and their parameters of efficacy and tolerability were considered as outcomes. Expert opinion: The one-handed 3.8-mm-diameter inserter of LNG-IUS 13.5 mg and 19.5 mg may be particularly suitable in nulliparous women. While LNG-IUSs 13.5, 19.5 mg and LNG 52 mg should be used by women simply looking for an effective contraceptive method for up to 3, 4 or 5 years, LNG-IUS 52 mg has also been approved for the treatment of heavy menstrual bleeding and endometrial protection during hormone replacement therapy. LNG-IUS 52 mg is ideal for women who are experiencing a certain hyperestrogenic hormonal environment, with heavy menstrual bleeding due to hormonal imbalances, adenomyosis or fibroids, in the case of symptomatic endometriosis or for endometrial protection during hormone estrogenic replacement therapy in non-hysterectomized women.

Medicine (Baltimore). 2018 Apr;97(15):e0376.

Intrauterine endometrial cyst after low uterine incision: A case report with literature review.

Yin W^1,2, Zhang J^1,2, Xu L^1,2, Luo L^1,2.

Abstract

RATIONALE:

During the surgical procedure, endometrial cells can be seeded into the wound edge of the uterine wall, developing into scar endometriosis. Due to the extremely low incidence, estimation of its prevalence is still unavailable. Even rarer might be the scar endometriosis in uterine cavity, to our best knowledge, a situation has not been reported yet.

PATIENT CONCERNS:

A 37-year-old woman complained of heavier and prolonged menstruation as well as pelvic pain during menses for more than 4 months. An endometrial cyst in diameter of 6 cm in uterine cavity was revealed by transvaginal ultrasound. Her surgical history was significant for 1 caesarean section and 1 abdominal myomectomy through transverse incision of lower uterine segment.

DIAGNOSES:

Space-occupying lesions in uterine cavity, moderate anemia and scar uterus.

INTERVENTIONS:

The hysteroscopy was performed and a multilocular cyst full of chocolate-like fluid was removed. Pathological examination confirmed endometrial glands in the removed cyst tissue.

OUTCOMES:

During the follow-up visits at 1 and 6 months after surgery, the patient denied any special discomfort. Her postoperative transvaginal ultrasound showed an enlarged uterus with no lesion in uterine cavity. To achieve a better surveillance, a 3-year period of follow-up after surgery at a 6-month interval was suggested.

LESSONS:

Intrauterine endometriosis should be considered in patients of pelvic surgery history with pelvic pain, menstrual disorder, and intrauterine cystic mass.

Reprod Sci. 2018 Jan 1

The Usefulness of CD34, PCNA Immunoreactivity, and Histopathological Findings for Prediction of Pain Persistence After the Removal of Endometrioma.

Usta A¹, Turan G², Altun E², Hocaoglu M³, Bulbul CB¹, Adali E¹.

Abstract

Endometriosis is an estrogen-dependent inflammatory disease that causes infertility and chronic pelvic pain. Ovarian endometrioma is the most common form of endometriosis, and conservative surgery is the main preferred therapeutic approach for endometrioma-associated symptoms. The aim of this study was to investigate the persistence of cyclic and noncyclic pelvic pain (NCPP) after endometrioma excision and their relationship to clinical and histopathological findings. In this prospective observational study, 41 symptomatic patients were evaluated for the presence of pain symptoms 3 to 6 months after endometrioma excision. Tissue specimens of endometrioma were collected during the operation and embedded in paraffin. The persistence of pain was 41.4%. Surgical excision of endometrioma significantly decreased NCPP and dysmenorrhea, but not dyspareunia ( P < .0001, P = .0001, and P = .25, respectively). Histopathological changes, including depth of endometriosis penetration into the cyst wall, the presence of macrophage infiltration, and vascularity of endometrioma cyst walls were significantly higher in patients with pain persistence than in patients without pain persistence ( P = .0034, P = .0042, and P = .0007, respectively). Moreover, proliferating cell nuclear antigen (PCNA) and CD34 immunoreactivity in both glandular and stromal cells and vascular endothelium were significantly higher in patients with pain persistence ( P = .0079 and P = .0025, respectively). Additionally, these histopathological changes and PCNA and CD34 immunoreactivity were significantly correlated with the persistence of NCPP and dysmenorrhea. The discovered differences in patients with endometrioma with or without pain persistence may indicate a possible relationship between endometrioma-associated pain and histopathological variability of endometrioma.

J Phys Ther Sci. 2017 Dec;29(12):2112-2115.

Efficacy of exercise on pelvic pain and posture associated with endometriosis: within subject design.

Awad E¹, Ahmed HAH², Yousef A³, Abbas R⁴.

Abstract

[Purpose] This study was carried out to determine the effect of an exercise program on pelvic pain and posture associated with endometriosis. [Subjects and Methods] This study was designed as repeated measures design that compared one group of 20 patients (age range 26-32 years) diagnosed by laparoscope as having mild or moderate endometriosis before, after 4 weeks, and after 8 weeks of exercise program. The exercise program parameters were based on the American College of Obstetricians and Gynecologists guidelines for exercise suitable for sedentary women. To assess the intensity of endometriosis pain, a present pain intensity scale was used. On the other hand, a raster stereography system was used to assess the posture. [Results] After 8 weeks of performing the exercise regimen, there was a statistically significant decrease in the patients’ pain intensity and thoracic kyphosis angle program in compared with pre treatment. [Conclusion] Ultimately it was proven that eight weeks of an exercise program is very effective in decreasing pain and postural abnormalities associated with endometriosis.

Cost Eff Resour Alloc. 2018 Apr 10;16:12.

Cost-effectiveness of the recommended medical intervention for the treatment of dysmenorrhea and endometriosis in Japan.

Arakawa I¹, Momoeda M^2,3, Osuga Y^4,3, Ota I^5,3, Koga K^4,3.

Abstract

BACKGROUND AND OBJECTIVE:

This study aims to assess the cost-effectiveness of early physician consultation and guideline-based intervention to prevent endometriosis and/or disease progression using oral contraceptive (OC) and progestin compared to follow-up of self-care for dysmenorrhea in Japan.

METHODS:

A yearly-transmitted Markov model of five major health states with four sub-medical states was constructed. Transition probabilities among health and medical states were derived from Japanese epidemiological patient surveys and converted to appropriate parameters for inputting into the model. The dysmenorrhea and endometriosis-associated direct costs included inpatient, outpatient visit, surgery, and medication (OC agents, over-the-counter drugs), etc. The utility measure for patients with phase I-IV endometriosis comprised a visual analogue scale. We estimated the cost per quality-adjusted life year (QALY) at a time horizon of 23 years. An annual discount rate at 3% for both cost and outcome was considered.

RESULTS:

The base case outcomes indicated that the intervention would be more cost-effective than self-care, as the incremental cost-effectiveness ratio (ICER) yielded 115,000 JPY per QALY gained from the healthcare payers’ perspective and the societal monetary value (SMV) was approximately positive 3,130,000 JPY, favoring the intervention in the cost-benefit estimate. A tornado diagram depicting the stochastic sensitivity analysis of the ICER and SMV from both the healthcare payers’ and societal perspectives confirmed the robustness of the base case. A probabilistic analysis resulting from 10,000-time Monte Carlo simulations demonstrated efficiency at willingness-to-pay thresholds in more than 90% of the iterations.

CONCLUSIONS:

The present analysis demonstrated that early physician consultation and guideline-based intervention would be more cost-effective than self-care in preventing endometriosis and/or disease progression for patients with dysmenorrhea in Japan.

Minerva Ginecol. 2018 Apr 11.

Fertility preservation in women with ovarian endometriosis.

Donnez J¹, García-Solares J², Dolmans MM³.

Abstract

Endometriosis is a frequently encountered benign gynecological disease that may be responsible for infertility. Treatment of endometriosis-associated infertility has been investigated using both medical and surgical therapeutic modalities. Therapy has essentially three main objectives: (i) to preserve and improve fertility, (ii) to reduce pain, and (iii) to delay recurrence. The aim of this paper is to focus on fertility preservation in women with severe endometriosis. In ovarian endometriosis-associated infertility, a medico-surgical approach remains the gold standard, but more and more papers are reporting a low ovarian reserve after laparoscopic cystectomy for endometriomas. Indeed, very frequently, normal ovarian tissue is excised together with the endometrioma wall, even if surgery is performed by experienced surgeons. Vitrification of oocytes should thus be considered in all patients at serious risk of future fertility impairment, particularly in case of recurrence after surgery or before any treatment likely to result in premature ovarian insufficiency (POI). This paper also describes techniques of ovarian tissue cryopreservation (slow-freezing) and reimplantation, which should be considered in case of recurrence risk.

Gynecol Endocrinol. 2018 Apr 12:1-6.

Does the type of GnRH analogue used, affect live birth rates in women with endometriosis undergoing IVF/ICSI treatment, according to the rAFS stage?

Drakopoulos P¹, Rosetti J¹, Pluchino N^2,3, Blockeel C^1,4, Santos-Ribeiro S^1,5, de Brucker M¹, Drakakis P⁶, Camus M¹, Tournaye H¹, Polyzos NP^1,7,8.

Abstract

Since the introduction of gonadotropin-releasing hormone (GnRH) antagonists, an extensive amount of literature investigating the role of the downregulation protocols on pregnancy outcomes has been published. However, these studies were mainly performed in the general infertile population where patients with endometriosis were often excluded or underrepresented. This study is a large retrospective cohort study including 386 endometriosis patients undergoing IVF/ICSI, who had been previously classified according to the rAFS system. Patients were stimulated either a long GnRH agonist or GnRH antagonist protocol. Depending on endometriosis stage, patients were divided into two groups: endometriosis stage I-II and endometriosis stage III-IV. Each group was subdivided, based on the type GnRH analog used. When comparing the GnRH agonist and antagonist groups, patients with endometriosis stage I-II, had a tendency toward higher β-hCG positive, clinical pregnancy, and live birth rates (42.8% vs. 26.7%; p = .07) in favor of GnRH agonist use. In endometriosis stage III-IV, no differences were observed between agonist and antagonist cycle in any of the pregnancy outcomes. Multivariate regression analysis did not reveal any significant predictor of live birth after adjusting for relevant confounders. Based on our findings, the chance to have a liveborn in endometriosis population seems not to be affected by the type of GnRH analog used, at least in advanced stages. Findings from stage I-II endometriosis cases merit consideration and further evaluation in a larger sample size is warranted.

J Psychosom Obstet Gynaecol. 2018 Apr 12:1-8.

Impact of coping strategies on quality of life of adolescents and young women with endometriosis.

González-Echevarría AM¹, Rosario E¹, Acevedo S², Flores I³.

Abstract

PURPOSE:

Endometriosis is a hormone-dependent, inflammatory, painful condition affecting 1 in 10 women during their reproductive years. The symptoms of endometriosis-dysmenorrhea, dyspareunia, infertility-negatively impact the quality of life (QoL) of the affected women. Few studies have been conducted on mental health and QoL impact in a younger endometriosis patient population (adolescents and young women). This study quantitative, cross-sectional study was designed to address this gap by ascertaining whether coping strategies may impact the QoL of this patient population.

METHODS:

After consent, participants (n = 24) completed a sociodemographic questionnaire, Beck Anxiety Inventory (BAI), Beck Depression Inventory II (BDI-II), Coping Strategies Inventory (CSI), Endometriosis Health Patient-5 (EHP-5) and Visual Analogue Scale (VAS).

RESULTS:

Participants reported the use of both positive and maladaptive strategies to deal with the symptomatology, which were associated with QoL levels and mental health status. Associations between QoL and maladaptive coping strategies (e.g. autocriticism, social withdrawal) were uncovered. Cognitive restructuring was identified as an adaptive coping strategy that impacts QoL positively.

CONCLUSION:

These results provide additional evidence showing that endometriosis symptoms substantially affect the psychological well-being of young patients and identify opportunities for interventions (e.g. cognitive behavioral, rational/emotive therapy) to implement coping styles leading to improved QoL.

Abdom Radiol (NY). 2018 Apr 12.

Splenosis: a great mimicker of neoplastic disease.

Tandon YK¹, Coppa CP², Purysko AS².

Abstract

Splenosis is a benign condition that can occur after splenic trauma or after surgery involving the spleen. These splenic implants are most often seen within the abdominal and pelvic cavities. On imaging, splenosis can be confused with multiple additional entities including metastatic disease, peritoneal carcinomatosis, peritoneal mesothelioma, abdominal lymphoma, renal cancer, hepatic adenomas, or endometriosis depending on its distribution. In all patients with history of splenic surgery or trauma, splenosis should be on the differential diagnosis of soft tissue nodules in the abdomen and pelvis, especially in the absence of systemic symptoms, to avoid unnecessary biopsy, chemotherapy, or surgery.

Curr Opin Obstet Gynecol. 2018 Apr 12.

Therapeutic strategies involving uterine stem cells in reproductive medicine.

Simoni M¹, Taylor HS.

Abstract

PURPOSE OF REVIEW:

The current review provides an update on recent advances in stem cell biology relevant to female reproduction.

RECENT FINDINGS:

Stem cells are undifferentiated cells that often serve as a reservoir of cells to regenerate tissue in settings or injury or cell loss. The endometrium has progenitor stem cells that can replace all of the endometrium during each menstrual cycle. In addition, multipotent endometrial cells replace these progenitor cells when depleted. Recruitment of stem cells from outside of the uterus occurs in setting of increased demand such as ischemia or injury. Bone marrow-derived multipotent stem cells are recruited to the uterus by estrogen or injury-induced expression of the chemokine CXCL12. In the setting of overwhelming injury, especially in the setting of low estrogen levels, there may be insufficient stem cell recruitment to adequately repair the uterus resulting in conditions such as Asherman syndrome or other endometrial defects. In contrast, excessive recruitment of stem cells underlies endometriosis. Enhanced understanding of stem-cell mobilization, recruitment, and engraftment has created the possibility of improved therapy for endometrial defects and endometriosis through enhanced manipulation of stem-cell trafficking. Further, the normal endometrium is a rich source of multipotent stem cells that can be used for numerous applications in regenerative medicine beyond reproduction.

SUMMARY:

A better understanding of reproductive stem-cell biology may allow improved treatment of endometrial disease such as Asherman syndrome and other endometrial receptivity defects. Inhibiting stem-cell mobilization may also be helpful in endometriosis therapy. Finally, endometrial derived multipotent stem cells may play a crucial role in cell therapy for regenerative medicine.

J Gynecol Obstet Hum Reprod. 2018 Apr 11.

Is training sufficient for ultrasound operators to diagnose deep infiltrating endometriosis and bowel involvement by transvaginal ultrasound?

Rosefort A¹, Huchon C², Estrade S¹, Paternostre A³, Bernard JP⁴, Fauconnier A⁵.

Abstract

OBJECTIVES:

To assess and compare the diagnostic accuracy of transvaginal ultrasonography (TVUS) by trained or untrained ultrasound operators in deep infiltrating endometriosis (DIE) imaging, for diagnosing DIE and bowel involvement.

METHODS:

This was an observational study of patients with clinically suspected DIE operated in a reference center. TVUS was performed pre-operatively by a trained or/and untrained ultrasound operator to search for DIE and rectal involvement. During surgery, DIE was diagnosed according to macroscopic and histological criteria. Sensitivity (Se), specificity (Sp) and c-index were calculated with 95% confidence intervals for trained and untrained operators, if TVUS results were significantly predictive of DIE and rectal involvement at p<0.05.

RESULTS:

115 patients were included: 100 (87%) had DIE and 34 (29.6%) had bowel involvement. TVUS was performed by a trained ultrasound operator for 70 patients and by an untrained one for 56 patients. When performed by a trained operator, TVUS significantly predicted DIE with a Se of 58% (95% CI, 46-70), a Sp of 87.5% (95% CI, 63-100) and a c-index of 0.73 (95% CI, 0.59-0.87). TVUS performed by an untrained operator was not significantly predictive of DIE (p=0.58). Rectal involvement was significantly predicted by TVUS performed by a trained operator with a Se of 40% (95% CI, 23-59), a Sp of 93% (95% CI, 86-100) and a c-index of 0.67 (95% CI, 0.56-0.77). None of the untrained ultrasound operators diagnosed a bowel involvement.

CONCLUSION:

TVUS is not sufficient to diagnose DIE and bowel involvement, in particular when performed by untrained ultrasound operators.

J Gynecol Obstet Hum Reprod. 2018 Apr 11.

Surgery using plasma energy for deep endometriosis: A quality of life assessment.

Delbos L¹, Bouet PE², Catala L², Lefebvre C², Teyssedou C³, Descamps P², Legendre G².

Abstract

OBJECTIVE:

The principal objective of our study was to assess women’s quality of life (QoL) after surgery for Deep Endometriosis (DE), according to the surgical technique used.

MATERIAL AND METHODS:

Qualitative single-center survey in the department of obstetrics and gynecology, Angers University Hospital Center, France. All women who underwent surgery for DE from January 2011 to December 2015 were contacted by phone. The Endometriosis Health Profile-5 score was used to assess QoL before and after the surgery. Fifty-two women (response rate=86%) were included and classified into 3 groups according to the surgical technique used: simple shaving, shaving exclusively or in part by plasma vaporization (plasma), and resection.

RESULTS:

The 3 groups were comparable for surgical history, preoperative QoL score, and characteristics of endometriotic lesions (size and site). All DE symptoms and QoL scores improved significantly after the surgery, all techniques combined (P<0.01). QoL scores for women who had plasma shaving or complete resection were significantly higher than those for women with simple shaving (respectively, 375 [225-800] and 450 [-50 to 725] vs 275 [-100 to 600]; P=0.04). Self-image significantly improved only in the plasma group (P=0.03). The complete resection group had longer hospitals stays than the other groups (P=0.001), as well as a higher surgical revision rate (23% vs 0%; P=0.02).

CONCLUSION:

Plasma and complete resection improved QoL similarly for women with DE, both more than shaving alone. The advantage of plasma vaporization lies in the lesser morbidity and better self-image, both better than in women with resection.

J Minim Invasive Gynecol. 2018 Apr 12.

Total Laparoscopic Ureteroneocystostomy for Ureteral Endometriosis: A Single-Center Experience of 160 Consecutive Patients.

Ceccaroni M¹, Ceccarello M², Caleffi G³, Clarizia R¹, Scarperi S¹, Pastorello M³, Molinari A³, Ruffo G⁴, Cavalleri S³.

Abstract

STUDY OBJECTIVE:

To investigate the efficacy of laparoscopic ureteroneocystostomy in patients with deep infiltrating endometriosis (DIE) with ureteral, parametrial, and bowel involvement.

DESIGN:

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

SETTING:

Tertiary referral center for endometriosis care.

PATIENTS:

One hundred and sixty patients with DIE underwent laparoscopic radical eradication and ureteroneocystostomy between January 2009 and December 2016.

INTERVENTIONS:

Laparoscopic nerve-sparing radical treatment with ureteroneocystostomy, parametrectomy, and, if necessary, segmental bowel resection.

MEASUREMENTS AND MAIN RESULTS:

Surgical eradication was radical, and ureteral endometriosis was histologically confirmed in all patients (45.6% intrinsic and 54.4% extrinsic). In 58.7% of patients, ureteroneocystostomy was performed with the psoas hitch technique. Bowel resection was performed in 121 patients (75.6%), and 115 of them had a concomitant ileostomy (71.9%). Unilateral parametrectomy was performed on the left side in 61.9% of patients and on the right side in 30% of patients, respectively, while bilateral parametrectomy was completed in 33 patients (20.6%). Postoperative complications were infrequent: 7 patients underwent reoperation (4.4%), 8 patients experienced fever (5%), 4 patients required blood transfusion (2.5%), 3 patients had intestinal fistulas (1.9%), and 24 patients experienced impaired bladder voiding (15%) after 6 months. Mean follow-up time was 20.5 months (1-60). The study reported good clinical and surgical results, with a regression of symptoms (p < .001) and recurrence of parametrial endometriosis of 1.2% that required opposite side ureteroneocystostomy.

CONCLUSION:

This is the largest documented series of patients with DIE undergoing laparoscopic radical eradication and ureteroneocystostomy. The collected data show that in patients with ureteral endometriosis, this technique is feasible, effective, safe, and provides good results in terms of relapses and symptom control.

Reprod Sci. 2018 Jan 1

Feasibility of Transabdominal Electrohysterography for Analysis of Uterine Activity in Nonpregnant Women.

Sammali F¹, Kuijsters NPM^1,2, Schoot BC^1,2,3, Mischi M¹, Rabotti C¹.

Abstract

PURPOSE:

Uterine activity plays a key role in reproduction, and altered patterns of uterine contractility have been associated with important physiopathological conditions, such as subfertility, dysmenorrhea, and endometriosis. However, there is currently no method to objectively quantify uterine contractility outside pregnancy without interfering with the spontaneous contraction pattern. Transabdominal electrohysterography has great potential as a clinical tool to characterize noninvasively uterine activity, but results of this technique in nonpregnant women are poorly documented. The purpose of this study is to investigate the feasibility of transabdominal electrohysterography in nonpregnant women.

METHODS:

Longitudinal measurements were performed on 22 healthy women in 4 representative phases of the menstrual cycle. Twelve electrohysterogram-based indicators previously validated in pregnancy have been estimated and compared in the 4 phases of the cycle. Using the Tukey honest significance test, significant differences were defined for P values below .05.

RESULTS:

Half of the selected electrohysterogram-based indicators showed significant differences between menses and at least 1 of the other 3 phases, that is the luteal phase.

CONCLUSION:

Our results suggest transabdominal electrohysterography to be feasible for analysis of uterine activity in nonpregnant women. Due to the lack of a golden standard, this feasibility study is indirectly validated based on physiological observations. However, these promising results motivate further research aiming at evaluating electrohysterography as a method to improve understanding and management of dysfunctions (possibly) related to altered uterine contractility, such as infertility, endometriosis, and dysmenorrhea.

Reprod Sci. 2018 Jan 1

Decreased Expression of HOXA10 May Activate the Autophagic Process in Ovarian Endometriosis.

Zheng J^1,2, Luo X^3,2, Bao J³, Huang X³, Jin Y⁴, Chen L⁴, Zheng F³.

Abstract

Autophagy is a survival process that maintains homeostasis in all eukaryotic cells. Recent studies show an abnormal autophagic activity in endometriosis, but the role of autophagy is controversial. Homeobox A10 (HOXA10) is a transcription factor necessary for embryonic and adult uterine development, and studies indicate that its expression decreases in endometriosis. Homeobox A10 may negatively regulate autophagy in endometriosis. To test this hypothesis, we measured the expression levels of autophagic biomarkers (beclin-1 and LC3-II) and HOXA10 proteins by Western blotting and messenger RNA (mRNA) by quantitative real-time polymerase chain reaction. Furthermore, we evaluated the serum cancer antigen 125 (CA125) levels by immunoassay. Most tested autophagic biomarker proteins and mRNAs were upregulated, whereas HOXA10 protein and mRNA were decreased in ovarian endometriomas compared with eutopic endometria of women with endometriosis and normal endometria. Compared with normal endometrium, only protein expression levels of autophagic biomarkers were increased in the eutopic endometrium of women with endometriosis. Moreover, HOXA10 was found to have a significant negative correlation with autophagy ( P < .01). Serum CA125 was at a high level in endometriosis and increased with elevated revised American Fertility Society staging (I-IV). There was a significant positive correlation between serum CA125 level and LC3-II protein level and/or LC3-II/LC3-I ratio ( P < .01) and a significant negative correlation between serum CA125 level and HOXA10 gene level ( P < .01). In conclusion, our studies support that the deficiency of HOXA10 may induce autophagy in endometriosis, and the relationship among CA125, autophagy, and HOXA10 in endometriosis requires additional research.

Mol Hum Reprod. 2018 Apr 11.

Exosomal miR-214 from endometrial stromal cells inhibits endometriosis fibrosis.

Wu D¹, Lu P¹, Mi X¹, Miao J¹.

Abstract

STUDY QUESTION:

Is it possible to improve fibrosis in endometriosis by microRNA-214 delivery in exosomes?

SUMMARY ANSWER:

Upregulation of miR-214 may inhibit fibrogenesis and its delivery by exosomes derived from ectopic endometrial stromal cells, offers an alternative therapeutic approach for endometriosis fibrosis.

WHAT IS KNOWN ALREADY:

Fibrosis is the primary pathological feature of endometriosis. MiR-214 plays an important role in fibrotic disease. Connective tissue growth factor (CTGF) is a critical fibrogenic mediator of miR-214. The expression of miR-214 is decreased in ectopic endometrial stromal cells compared with normal endometrial stromal cells. miRNAs are a natural cargo of exosomes and these could be exploited as carriers of miRNA in replacement therapy.

STUDY DESIGN, SIZE, DURATION:

Paired eutopic and ectopic endometrial tissue samples were obtained from 10 women with ovarian endometrioma. Endometrial stromal cells and epithelial cells from both were cultured in vitro. RT-PCR,western blot and immunohistochemistry were used to study the effect of transfection with miR-214 mimics on CTGF expression and fibrogenesis respectively, with and without TGFβ stimulation. Exosomes were isolated from ectopic endometrial stromal cells and Endometrioma tissue was isolated from 4 patients, dispersed an injected (ip) into nude mice and allowed to implant. The mice were treated with miR-214-enriched exosomes or controls to confirm the effect of inhibiting CTGF overexpression on endometriosis fibrosis.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

The primary ectopic endometrial stromal cells were transfected with miR-214 mimics. The levels of miR-214, CTGF and fibrotic markers were measured by RT-PCR and Immunohistochemistry. A mouse model of endometriosis was established by ip injection of human ectopic endometrial tissues into nude mice. MiR-214-enriched exosomes were injected into the mice and endometriotic lesions were measured on day 28. Changes in fibrosis of the endometriotic implants were studied by histopathological staining.

MAIN RESULTS AND THE ROLE OF CHANCE:

CTGF and fibrotic markers up-regulation in endometriosis is associated with a reciprocal down-regulation of miR-214. By using miR-214 mimics and antagomirs to investigate expression of fibrotic markers, we found that increased production of miR-214 reduced Collagen αI and CTGF expression in endometriosis stromal and endometrial epithelial cells in response to fibrosis-inducing stimuli (p < 0.001 versus non-treatment). Ectopic endometrial stromal cells yielded nano-sized exosomes which expressed miR-214. Loading exosomes with miR-214 mimics and injecting them into an experimental endometriosis mouse model resulted in a decrease in the expression of fibrosis-associated proteins (p < 0.001 versus PBS control group).

LARGE SCALE DATA:

N/A.

LIMITATIONS REASONS FOR CAUTION:

We only isolated exosomes from ectopic endometrial stromal cells, whether this is the optimum source requires further study.

WIDER IMPLICATIONS OF THE FINDINGS:

Upregulation of miRNA-214 potentially offers an alternative therapeutic approach for endometriosis fibrosis.

STUDY FUNDING/COMPETING INTEREST(S):

This work was supported by grants from the National Natural Science Foundation of China (Grant No. 81771549 Jinwei Miao). The authors declare that there is no conflict of interest.

Pan Afr Med J. 2018 Jan 11;29:22.

Endométriome ombilical: à propos d’un cas et revue de la littérature: Umbilical endometrioma: a case report and literature review.

Sow O¹, Valentin W², Cheikh D³, Denis B⁴, Thiapato FS³, Ibrahima D³, Kane GSM².

Abstract

Endometriosis is defined as the implantation of endometrial tissue outside of the uterine cavity. It affects approximately 10% of women of childbearing age. Umbilical endometriosis is rare and its pathophysiology is poorly known. We report the case of a 42-year old nulliparous female patient with a 5-year history of myomectomy, presenting with cyclic pain associated with umbilical mass. The diagnosis of umbilical endometrioma was made and confirmed by the histological examination of the surgical specimen. Treatment was based on wide excision of the mass associated with pelvis exploration and umbilical plasty.

Turk J Obstet Gynecol. 2018 Mar;15(1):33-38.

Post-cesarean scar endometriosis.

Yıldırım D¹, Tatar C¹, Doğan O², Hut A¹, Dönmez T³, Akıncı M¹, Toptaş M⁴, Bayık RN⁵.

Abstract

OBJECTIVE:

Endometriosis is seen in women during their reproductive period, where stromal tissue and functional endometrial glands of the uterus are observed outside the uterine cavity. In this study, we aimed to identify the clinical characteristics of our patients who underwent surgery with scar endometriosis and to discuss the surgical results in light of the literature.

MATERIALS AND METHODS:

A total of 24 patients who underwent surgery and diagnosed as having endometriosis as the result of a pathologic examination were retrospectively evaluated.

RESULTS:

The mean age of the patients was 31 years. Thirteen presented to general surgery and 11 presented to gynecology outpatient clinics. The pain was cyclical in 19 patients. There was history of cesarean section in 9 patients, twice in 12, and 3 times in three patients. The mean diameter was 39.1 mm on ultrasound, and 37.5 mm on magnetic resonance imaging. Endometriosis was on the left side of the incisions in 13, whereas it was on the right in 11. The mean weight of the lesions was 61.6 grams.

CONCLUSION:

The occurrence of endometriosis is supported by the iatrogenic implantation theory. In the event of a mass in the abdominal wall, previous obstetric and gynecologic operations and a history of a painful mass during menstruation periods must be questioned. In the treatment of scar endometriosis, excision is required by obtaining secure margins. If diagnosis can be established preoperatively, unnecessary surgeries can prevented.

Turk J Obstet Gynecol. 2018 Mar;15(1):50-59.

Tumor necrosis factor alfa and interleukin 1 alfa induced phosphorylation and degradation of inhibitory kappa B alpha are regulated by estradiol in endometrial cells.

Arlıer S^1,2, Kayışlı ÜA¹, Arıcı A^3,4.

Abstract

OBJECTIVE:

When bound to the inhibitory kappa B (IкB) protein, the transcription factor nuclear factor kappa B (NF-кB) remains inactively in the cytoplasm. Activated NF-кB upregulates the gene expression of many chemokines including monocyte chemoattractant protein-1 and interleukin (IL)-8. We hypothesized that estrogen may regulate IкB phosphorylation and degradation thus influencing NF-кB-dependent gene expression. Regulation of chemokines by estrogen is different in uterine endometrial cells when compared to ectopic endometrial cells of endometriosis.

MATERIALS AND METHODS:

We investigated the in vivo expression of IкB in normal endometrium and in eutopic and ectopic endometrium of women with endometriosis. We then studied in cultured endometrial cells to assess the effects of estradiol on IкB and NF-кB function.

RESULTS:

Normal endometrium from mid-late proliferative phase revealed the strongest IкB immunoreactivity throughout the cycle (p<0.05). When compared to paired homologous eutopic endometrium, ectopic endometrium revealed significantly less immunoreactivity for IкB (p<0.05). Moreover, estradiol induced a decrease in tumor necrosis factor-and IL-1-induced IкB phosphorylation, and also decreased the levels of active-NF-кB (p<0.05).

CONCLUSION:

Our results support the conclusion that one pathway for estradiol-mediated NF-кB inhibition occurs through the down-regulation of IкB phosphorylation. We propose that the estradiol-induced regulation of IкB and consequent reduction in active-NF-кB may affect inflammatory responses in human endometrial cells.

GE Port J Gastroenterol. 2018 Mar;25(2):86-90.

Endometriosis: A Rare Cause of Large Bowel Obstruction.

Alexandrino G¹, Lourenço LC¹, Carvalho R¹, Sobrinho C², Horta DV¹, Reis J¹.

Abstract

Large bowel obstruction can result in significant morbidity and mortality, especially in cases of acute complete obstruction. There are many possible causes, the most common in adults being colorectal cancer. Endometriosis is a benign disease, and the most affected extragenital location is the bowel, especially the rectosigmoid junction. However, transmural involvement and acute occlusion are very rare events. We report an exceptional case of acute large bowel obstruction as the initial presentation of endometriosis. The differential diagnosis of colorectal carcinoma may be challenging, and this case emphasizes the need to consider intestinal endometriosis in females at a fertile age presenting with gastrointestinal symptoms and an intestinal mass causing complete large bowel obstruction.

Int J Cancer. 2018 Apr 16.

Impact of iASPP on chemoresistance through PLK1 and autophagy in ovarian clear cell carcinoma.

Chan KK¹, Wong OG¹, Wong ES¹, Chan KK², Ip PP¹, Tse KY², Cheung AN^1,3.

Abstract

Ovarian clear cell carcinoma (OCCC) is a type of epithelial ovarian cancer that is strongly associated with endometriosis, resistance against conventional chemotherapy and thus poorer prognosis. The expression of inhibitory member of the ASPP family proteins (iASPP) and Polo-like kinase (PLK)1 were significantly higher in OCCC compared to benign cystadenomas and endometriosis. Both protein expressions were found to correlate with chemoresistance in patients with OCCC while high iASPP expression alone was significantly associated with a poor patient survival. The growth of OCCC cell lines, OVTOKO and KK, were inhibited after iASPP silencing. Such effect was related to senescence triggering as evidenced by increased SA-β-Gal staining and p21^WAF1/Cip1 expression. Moreover, knockdown of iASPP induced PLK1 downregulation, whereas either genes’ silencing sensitized the cells in response to cisplatin treatment. More prominent apoptosis was induced by cisplatin in OCCC cells after the knockdown of either iASPP or PLK1 as evidenced by the formation of more cleaved caspase 3. Heightened chemosensitivity to cisplatin after iASPP knockdown was further demonstrated in in vivo xenograft model. Additionally, both iASPP and PLK1 were shown to regulate autophagic flux as the induction of LC3B-II and LC3 puncta were much less in OCCC cells with either knockdown. Importantly, inhibition of autophagy also enhanced chemosensitivity to cisplatin in OCCC cells. These findings strongly imply that iASPP and PLK1 affect the chemoresistance of OCCC via the regulation of autophagy and apoptosis. Both iASPP and PLK1 can be potential therapeutic targets for treating OCCC in combination with conventional chemotherapy. (247 words) This article is protected by copyright. All rights reserved.

Comp Med. 2018 Apr 2;68(2):177-181.

Repair of a Large Ventral Hernia in a Rhesus Macaque (Macaca mulatta) by Using an Abdominal Component Separation Technique.

Kempton SJ¹, Israel JS², Capuano Iii S³, Poore SO².

Abstract

Ginekol Pol. 2018;89(3):125-134.

HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis.

Osiński M, Wirstlein P, Wender-Ożegowska E, Mikołajczyk M, Jagodziński PP, Szczepańska M¹.

Abstract

OBJECTIVES:

The development of endometriosis is associated with changes in the expression of genes encoding the 3β-hydroxysteroid dehydrogenase type II (HSD3B2) and 17β-hydroxysteroid dehydrogenase type II (HSD17B2), estrogen receptors 1 (ESR1) and 2 (ESR2) and the androgen receptor (AR). However, little is known about the expression of HSD3B2, HSD17B1, HSD17B2, ESR1 ESR2 and AR during the endometrial phases in eutopic endometrium from infertile women with endometriosis.

MATERIAL AND METHODS:

Using RT-qPCR analysis, we assessed the expression of the studied genes in the follicular and luteal phases in eutopic endometrium from fertile women (n = 17) and infertile women (n = 35) with endometriosis.

RESULTS:

In the mid-follicular eutopic endometrium, we observed a significant increase in HSD3B2 transcript levels in all infertile women with endometriosis (p = 0.003), in infertile women with stage I/II endometriosis (p = 0.008) and in infertile women with stage III/IV endometriosis (p = 0.009) compared to all fertile women. There was a significant increase in ESR1 tran-scripts in all infertile women with endometriosis (p = 0.008) and in infertile women with stage I/II endometriosis (p = 0.019) and in infertile women with stage III/IV endometriosis (p = 0.023) compared to all fertile women. In the mid-luteal eutopic endometrium, we did not observe significant differences in HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR transcripts between infertile women with endometriosis and fertile women.

CONCLUSIONS:

Observed significant increase in HSD3B2 and ESR1 transcripts in follicular eutopic endometrium from infer-tile women with endometriosis may be related to abnormal biological effect of E2 in endometrium, further affecting the development of human embryos.

Arch Iran Med. 2018 Feb 1;21(2):61-66.

Maternal Anthropometric Characteristics and Adverse Pregnancy Outcomes in Iranian Women: A Confirmation Analysis.

Hoorsan H¹, Alavi Majd H², Chaichian S³, Mehdizadehkashi A⁴, Hoorsan R⁵, Akhlaqghdoust M⁶, Moradi Y⁶.

Abstract

BACKGROUND:

Adverse pregnancy outcome are frequent in developing countries. Pregnancy outcomes are influenced by numerous factors. It seems that maternal anthropometric indices are among the most important factors in this era. The aim of this study was to determine any association between maternal anthropometric characteristics and adverse pregnancy outcomes in Iranian women and provide a predictive model by using factors affecting birth weight (BW) via the pathway analysis.

METHODS:

This study was performed in Alborz province between September 2014 and December 2016. In this cross-sectional study, 1006 pregnant women who had the study criteria were selected from 1500 pregnant women. The data were collected in 2 phases: at their first prenatal visit and during the postpartum period. Demographic data, history of previous pregnancy, fundal height (FH), gestational weight gain (GWG), and abdominal circumference (AC) were recorded. Pathway (path) analysis was used to assess effective factors on pregnancy outcomes.

RESULTS:

The mean and standard deviation of participant age at delivery was 25.97 ± 5.71 years. Overall, 4.6% of infants were low BW (LBW) and 5.8% had macrosomia. The final model, with a good fit accounting for 22% of BW variance, indicated that AC and FH (both P < 0.001), and pre-pregnancy body mass index (BMI) (P = 0.01) had positive direct effect on BW, while pre-pregnancy BMI and GWG (both P < 0.001) affected BW indirectly through their effect on FH and AC.

CONCLUSION:

Based on the path analysis model, FH and AC of neonates with the greatest impact on BW, could be predicted by mother’s BMI before pregnancy and weight gain during pregnancy. Therefore, close observation during prenatal care can reduce the risk of abnormal BW.

Dis Colon Rectum. 2018 Apr 16.

Functional Outcomes After Rectal Resection for Deep Infiltrating Pelvic Endometriosis: Long-term Results.

Erdem S¹, Imboden S², Papadia A², Lanz S², Mueller MD², Gloor B¹, Worni M¹.

Abstract

BACKGROUND:

Curative management of deep infiltrating endometriosis requires complete removal of all endometriotic implants. Surgical approach to rectal involvement has become a topic of debate given potential postoperative bowel dysfunction and complications.

OBJECTIVE:

This study aims to assess long-term postoperative evacuation and incontinence outcomes after laparoscopic segmental rectal resection for deep infiltrating endometriosis involving the rectal wall.

DESIGN:

This is a retrospective study of prospectively collected data.

SETTINGS:

This single-center study was conducted at the University Hospital of Bern, Switzerland.

PATIENTS:

Patients with deep infiltrating endometriosis involving the rectum undergoing rectal resection from June 2002 to May 2011 with at least 24 months follow-up were included.

MAIN OUTCOME MEASURES:

Aside from endometriosis-related symptoms, detailed symptoms on evacuation (points: 0 (best) to 21 (worst)) and incontinence (0-24) were evaluated by using a standardized questionnaire before and at least 24 months after surgery.

RESULTS:

Of 66 women who underwent rectal resection, 51 were available for analyses with a median follow-up period of 86 months (range: 26-168). Forty-eight patients (94%) underwent laparoscopic resection (4% converted, 2% primary open), with end-to-end anastomosis in 41 patients (82%). Two patients (4%) had an anastomotic insufficiency; 1 case was complicated by rectovaginal fistula. Dysmenorrhea, nonmenstrual pain, and dyspareunia substantially improved (p < 0.001 for all comparisons). Overall evacuation score increased from a median of 0 (range: 0-11) to 2 points (0-15), p = 0.002. Overall incontinence also increased from 0 (range: 0-9) to 2 points (0-9), p = 0.003.

LIMITATIONS:

This study was limited by its retrospective nature and moderate number of patients.

CONCLUSIONS:

Laparoscopic segmental rectal resection for the treatment of deep infiltrating endometriosis including the rectal wall is associated with good results in endometriotic-related symptoms, although patients should be informed about possible postoperative impairments in evacuation and incontinence. However, its clinical impact does not outweigh the benefit that can be achieved through this approach. See Video Abstract at http://links.lww.com/DCR/A547.

Case Rep Gastrointest Med. 2018 Feb 14.

Postmenopausal Deep Infiltrating Endometriosis of the Colon: Rare Location and Novel Medical Therapy.

Snyder BM¹, Beets JW², Lessey BA³, Horton SRW⁴, Abrams GA².

Abstract

We report an uncommon case of deep infiltrating endometriosis of the colon presenting as iron deficiency anemia nine years after hysterectomy with bilateral salpingo-oophorectomy. The endometrial implant was found at the hepatic flexure, an exceedingly rare location for endometriosis invasion with no cases distinctly reported in the literature. Additionally, the presentation of gastrointestinal endometriosis as iron deficiency anemia is not well documented in the literature. Instead of surgery, we prescribed a novel medical therapeutic approach using conjugated estrogen-bazedoxifene to antagonize the proliferative effects of estrogen on endometrial tissue. After five months of therapy and repeat colonoscopy, no evidence of endometrial tissue remained in the hepatic flexure.

Fondazione Italiana Endometriosi

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