BMJ Case Rep. 2018 Jan 23;2018. pii: bcr-2017-222431. doi: 10.1136/bcr-2017-222431.
Endometriosis presenting as a vaginal mass.
A 43-year-old woman with an anterior vaginal wall mass was referred to gynaecology outpatient for diagnosis and management. Clinical assessment was indicative of a urethral diverticulum, however MRI and ultrasound imaging suggested a Gartner’s duct cyst. Following excision of the lesion, histology revealed evidence of an endometriotic cyst. The patient had no other symptoms of endometriosis and remained asymptomatic 3 months following excision. This case highlights the widespread locations in which endometrial tissue can be found, and therefore the range of symptomatology. This in turn lends itself to diagnostic difficulty without histological confirmation.
Virchows Arch. 2018 Jan 24. doi: 10.1007/s00428-018-2295-3. [Epub ahead of print]
Chondroid nodule in the female peritoneum arises from normal tissue and not from teratoma or conception product.
The pathogenesis of benign-looking cartilaginous tissue within the peritoneum is unknown. Chondroid metaplasia of subcoelomic mesenchyme has been suggested, as has been the case for other gynecological diseases such as endometriosis, peritoneal leiomyomatosis, or gliomatosis peritonei, but has never been proven. Chondroid nodules in the peritoneum may represent either teratomatous tissue, fetal rests from a conception product, or metaplasia of pluripotent mesenchymal cells. Herein, the unique genetic characteristics of ovarian teratomas (homozygous at many polymorphic microsatellite loci) versus normal tissues (heterozygous at the same loci) were used to investigate the origin of chondroid nodules in the peritoneum. DNA samples extracted from paraffin-embedded normal peritoneal tissue and chondroid peritoneal nodules from two patients were studied. In both cases, chondroid and normal tissue showed heterozygosity at each informative microsatellite locus on different chromosomes, with a profile similar to the mother. These results indicate that peritoneal chondroid nodules arise within the peritoneum, presumably from pluripotent mesodermal stem cells, and are not related to teratomatous proliferation, or previous pregnancy. This finding shows once again the plasticity and metaplastic potential of stem cells within the peritoneal cavity.
Obstet Gynecol Sci. 2018 Jan;61(1):111-117. doi: 10.5468/ogs.2018.61.1.111. Epub 2017 Dec 18.
Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma.
Endometriosis is a common and recurring gynecologic disease which have afflicting females of reproductive age. We investigated the efficacy of long-term, post-operative use of dienogest for ovarian endometrioma.
We studied 203 patients who had undergone laparoscopic or robotic surgery for ovarian endometrioma, and were administrated dienogest 2 mg/day beginning in July of 2013, and continuing. We evaluated side effects of dienogest and ultrasonography was performed every 6 months to detect potential recurrence of endometrioma (2 cm) in these post-surgical patients.
The follow-up observation periods were 30.2±20.9 months from surgery. The mean age was 34.1±7.2 years old. The mean diameter of pre-operative endometrioma was 5.6±3.0 cm2. One hundred eighty-two (89.7%) women received dienogest continuously for 12.0±7.1 months. Of the subjects, 21 (10.3%) patients discontinued dienogest at 2.4±1.0 months. The most common side effect when dienogest was discontinued was abnormal uterine bleeding. The occurrence rate of vaginal bleeding was 15.8%, a number which did not differ significantly in patients with/without post-operative gonadotropin releasing hormone agonist administration. The other side effects were gastrointestinal trouble including constipation, acne, headache, depression, hot flush, weight gain, and edema. However, no serious adverse events or side effects were documented and recurrent endometriomas were diagnosed in 3 patients (1.5%).
The data indicates that dienogest was both tolerable and safe for long-term use as prophylaxis in an effort to obviate the recurrence of ovarian endometrioma post-operatively, as well as potential need for surgical re-intervention.
Obstet Gynecol Sci. 2018 Jan;61(1):142-146. doi: 10.5468/ogs.2018.61.1.142. Epub 2017 Dec 13.
Menstrual characteristics in Korean women with endometriosis: a pilot study.
This study aimed to determine whether the menstrual characteristics are different in Korean women with or without ovarian endometrioma.
We selected 95 premenopausal women aged below 39 years who underwent laparoscopic surgery for ovarian endometrioma (n=46) or other benign ovarian tumors (n=49) between April 2016 and February 2017. We excluded those with uterine diseases that could potentially affect the menstrual characteristics and those on anticoagulants or hormonal medication. At admission, menstrual characteristics such as cycle length, cycle regularity, and menstrual duration, were collected. In addition, amount of menstrual bleeding and severity of dysmenorrhea were recorded using a pictorial blood loss assessment chart (PBAC) and visual analogue scale, respectively.
Age and parity were similar in both women with ovarian endometrioma and women with other benign ovarian tumors. Body mass index (BMI) was significantly lower (median, 20.9 vs. 22.1 kg/m2; P=0.031) in women with ovarian endometrioma. The amount of menstrual bleeding (median PBAC score, 183 vs. 165), menstrual duration (median, 6 vs. 6 days), and cycle length in women with regular cycle (median, 29.0 vs. 29.2 days) were not different between the 2 groups. Pain score was significantly higher (median, 4 vs. 3; P=0.005) in women with ovarian endometrioma.
We found that the menstrual characteristics between women with ovarian endometrioma and women with other benign ovarian tumors were similar. We also observed that low BMI may be one of the risk factor for endometriosis.
J Minim Invasive Gynecol. 2018 Jan 31. pii: S1553-4650(18)30058-X. doi: 10.1016/j.jmig.2018.01.019. [Epub ahead of print]
Does Computed Tomography-Based Virtual Colonoscopy Improve the Accuracy of Preoperative Assessment Based on Magnetic Resonance Imaging in Women Managed for Colorectal Endometriosis?
To evaluate whether combining computed tomography-based virtual colonoscopy (CTC) with magnetic resonance imaging (MRI) improves preoperative assessment of colorectal endometriosis.
Retrospective study using prospectively recorded data (Canadian Task Force classification II-2).
University tertiary referral center.
Seventy-one women treated for colorectal endometriosis managed between June 2015 and May 2016.
Patients included in our study underwent colorectal surgery for deep endometriosis infiltrating the rectum or the sigmoid colon and had preoperative assessment using MRI and CTC. To establish the correlation between preoperative and intraoperative findings, the concordance kappa index was used.
MEASUREMENTS AND MAIN RESULTS:
Preoperative data provided by MRI, CTC, and a combination of both were compared with intraoperative findings. All 71 patients had a total of 105 endometriotic intestinal lesions intraoperatively confirmed. Some 71.2% of rectal nodules and 60.0% of sigmoid nodules infiltrated the muscularis propria of the intestinal wall, with most infiltrating between 25% and 50% of the rectal circumference; 73% of rectal nodules and 96% of sigmoid nodules led to varying degrees of stenosis. The concordance between intraoperative and preoperative findings concerning the presence of rectal nodules was high, at .88 when associating CTC with MRI, whereas each imaging technique taken individually provided lower concordance coefficients. In our study 80.3% of patients underwent the procedure that had been preoperatively planned.
Our study suggests that associating MRI with CTC leads to improved accuracy in preoperative assessment of colorectal endometriosis and in subsequent preoperative choice of surgical procedures on the digestive tract.
J Minim Invasive Gynecol. 2018 Jan 31. pii: S1553-4650(18)30059-1. doi: 10.1016/j.jmig.2018.01.020. [Epub ahead of print]
Pain is an Independent Risk Factor for Failed Global Endometrial Ablation.
To determine whether pain, as part of an indication for global endometrial ablation, is an independent risk factor for failure.
Retrospective cohort study (Canadian Task Force classification II-2).
Academic-affiliated community hospital.
Women undergoing global endometrial ablation with radiofrequency ablation (RFA), hydrothermablation (HTA), or uterine balloon ablation (UBA) between January 2003 and December 2015.
Procedure failure was defined as subsequent hysterectomy after the index ablation.
MEASUREMENTS AND MAIN RESULTS:
A total of 5818 women who underwent an endometrial ablation were identified, including 3706 with RFA (63.7%), 1786 with HTA (30.7%), and 326 with UBA (5.6%). Of the 5818 ablations, 437 (7.5%) involved pain (i.e., pelvic pain, dysmenorrhea, dyspareunia, lower abdominal pain, endometriosis, or adenomyosis) before ablation, along with abnormal uterine bleeding. Pain as part of the preoperative diagnoses before endometrial ablation was a significant risk factor for subsequent hysterectomy compared with all other diagnoses (19.2% vs 13.5%; p = .001). Consistent with previous studies, women who underwent ablation at an older age were less likely to fail, which held true even when one of the indications for ablation was related to pain (odds ratio, 0.96/year; 95% confidence interval, 0.95-0.97). When the pathology reports of women who underwent a hysterectomy were examined, women in the pain group had lower rates of adenomyosis than women without pain (38.1% vs 50.1%; p = .04). However, there was a trend toward a higher rate of endometriosis on pathology reports (14.3% vs 8.7%; p = .09) and even higher rates of visualized endometriosis identified by operative reports in women who had pain before their ablation (42.9% vs 15.8%; p < .001). Patients who had pain before their ablation were less likely to have myomas/polyps (p = .01).
Pelvic pain before global endometrial ablation is an independent risk factor for failure.
Hum Reprod Update. 2018 Jan 25. doi: 10.1093/humupd/dmy001. [Epub ahead of print]
Basic mechanisms of vascularization in endometriosis and their clinical implications.
Vascularization is a major hallmark in the pathogenesis of endometriosis. An increasing number of studies suggests that multiple mechanisms contribute to the vascularization of endometriotic lesions, including angiogenesis, vasculogenesis and inosculation.
OBJECTIVE AND RATIONALE:
In this review, we provide an overview of the basic mechanisms of vascularization in endometriosis and give special emphasis on their future clinical implications in the diagnosis and therapy of the disease.
Literature searches were performed in PubMed for English articles with the key words ‘endometriosis’, ‘endometriotic lesions’, ‘angiogenesis’, ‘vascularization’, ‘vasculogenesis’, ‘endothelial progenitor cells’ and ‘inosculation’. The searches included both animal and human studies. No restriction was set for the publication date.
The engraftment of endometriotic lesions is typically associated with angiogenesis, i.e. the formation of new blood vessels from pre-existing ones. This angiogenic process underlies the complex regulation by angiogenic growth factors and hormones, which activate intracellular pathways and associated signaling molecules. In addition, circulating endothelial progenitor cells (EPCs) are mobilized from the bone marrow and recruited into endometriotic lesions, where they are incorporated into the endothelium of newly developing microvessels, referred to as vasculogenesis. Finally, preformed microvessels in shed endometrial fragments inosculate with the surrounding host microvasculature, resulting in a rapid blood supply to the ectopic tissue. These vascularization modes offer different possibilities for the establishment of novel diagnostic and therapeutic approaches. Angiogenic growth factors and EPCs may serve as biomarkers for the diagnosis and classification of endometriosis. Blood vessel formation and mature microvessels in endometriotic lesions may be targeted by means of anti-angiogenic compounds and vascular-disrupting agents.
The establishment of vascularization-based approaches in the management of endometriosis still represents a major challenge. For diagnostic purposes, reliable angiogenic and vasculogenic biomarker panels exhibiting a high sensitivity and specificity must be identified. For therapeutic purposes, novel compounds selectively targeting the vascularization of endometriotic lesions without inducing severe side effects are required. Recent progress in the field of endometriosis research indicates that these goals may be achieved in the near future.
J Med Case Rep. 2018 Jan 30;12(1):21. doi: 10.1186/s13256-017-1537-3.
Intestinal endometriosis combined with colorectal cancer: a case series.
Intestinal endometriosis is a common benign disease among menstruating women that affects the intestinal tract.
This case report presents seven Japanese cases of intestinal endometriosis with colorectal cancer treated by laparoscopic surgery. Five of the seven cases reported here are women presenting with bowel obstruction due to colorectal endometriosis with colorectal cancer. It can be confused with serious lesions such as advanced colorectal cancer with peritoneal involvement or invasion of adjacent organs (T4).
Therefore, we should consider the probability that the cause of bowel obstruction is not T4 but intestinal endometriosis. For surgical treatment, we recommend laparoscopic surgery for colorectal resection because of its benefits of differential diagnosis of T4, preserving fertility, and preventing excessive surgical stress. We performed laparoscopic resection in seven patients with intestinal endometriosis and colorectal cancer. These cases demonstrate the difficulty of establishing a differential diagnosis of intestinal endometriosis with colorectal cancer from T4.
Clin Interv Aging. 2018 Jan 4;13:73-79. doi: 10.2147/CIA.S147757. eCollection 2018.
The effects of injecting intra-articular platelet-rich plasma or prolotherapy on pain score and function in knee osteoarthritis.
Osteoarthritis (OA) is a chronic joint disease that usually occurs in older people and leads to pain and disabilities. OA treatment ranges from drug therapy to surgery. Drug and rehabilitation therapy are preferred over surgery, and, especially, there is a tendency toward compounds causing regenerative changes in the knee joint. In the present study, the effects of platelet-rich plasma (PRP) injection and prolotherapy (PRL) were examined on the level of pain and function of the knee joint in patients with OA.
After fulfilling the inclusion criteria and signing the informed consent form, 42 patients with knee OA were scheduled for intra-articular injection in the present randomized, double-blind, clinical trial. Following admission to the operating pain room, the condition of the patient’s knee was evaluated first via the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and, then, ultrasound-guided knee injection was done. Accordingly, patients in the PRP therapy group received 7 mL PRP solution and those in the PRL group received 7 mL 25% dextrose. Using the WOMAC, levels of pain and knee function were evaluated and recorded for each patient immediately prior to the first injection as well as at 1 month (immediately prior to the second injection), 2 months (a month after the second injection), and 6 months later. Data collected were analyzed using the SPSS v.20.
During the first and second months, a rapid decrease in the overall WOMAC score was observed in both groups. The overall WOMAC score increased at the sixth month, but was lower than the overall WOMAC score in the first month. Statistical analysis indicated that the overall WOMAC score significantly decreased in both groups of patients over 6 months.
Results of the present study suggested a significant decrease in the overall WOMAC score of patients who undergo either PRP therapy or PRL. This positive change in the overall WOMAC score led to an improvement in the quality of life of patients with knee OA shortly after the first injection. PRP injection is more effective than PRL in the treatment of knee OA.
Turk J Obstet Gynecol. 2017 Dec;14(4):233-237. doi: 10.4274/tjod.55453. Epub 2017 Dec 30.
Could the female-to-male transgender population be donor candidates for uterus transplantation?
To evaluate the eligibility of female-to-male (FtM) transgender people as donor candidates with regard to histologic, surgical, and social aspects.
MATERIALS AND METHODS:
In this prospective cohort study, 31 FtM transgender people underwent standard hysterectomy and bilateral salpingo-oophorectomy for gender reassignment upon their request. The pelvic viscera of the transgender people was intraoperatively observed and the histology of the removed uteri were evaluated for fertility capacity and procurement surgery. A questionnaire was administered to explore their attitude towards uterus donation.
The mean ± standard deviation age was 28.5±5 years. The median duration of testosterone supplementation was 2.4 years; therefore, they all had irregular menstrual periods during this therapy. None had any previous abdominal surgery or additional morbidity. The mean uterine volume was 138±48 cm3. No adenomyosis, endometriosis, polyps, adhesions or uterine anomalies were either observed or reported. Endometrial histology was reported as proliferative (58%), atrophic (29%), and secretory (13%) pattern. Of the 31 transgender people, 30 (96.7%) had a positive attitude; only one had no opinion at the beginning. After detailed information about the procedure was given, 26 (84%) still wanted to volunteer for donation, but 4 (12%) changed their opinion to negative (p=0.12, McNemar test).
The proposal of the FtM transgender population as uterus donor is a hypothetical model that has not been experienced before. Nevertheless, our experience revealed that the FtM transgender population would be good candidates socially, legally, and biologically.
Turk J Obstet Gynecol. 2017 Dec;14(4):238-242. doi: 10.4274/tjod.56588. Epub 2017 Dec 30.
The efficacy of laparoscopic presacral neurectomy in dysmenorrhea: is it related to the amount of excised neural tissue?
To assess the correlation between the number of excised neural fibers and degree of pain relief following laparoscopic presacral neurectomy (LPSN).
MATERIALS AND METHODS:
In this before and after study, 20 patients with severe midline dysmenorrhea [Visual Analogue Scale (VAS) >80 mm] unresponsive to medical therapy were consecutively enrolled. All patients underwent LPSN. The superior hypogastric plexus was excised and sent for histologic confirmation. Two pathologists counted the number of neural fibers in the surgically removed tissue. VAS was used for pain assessment before and 2nd, 3rd, 6th, and 12th months after the operations.
Out of the initial 20 patients undergoing LPSN, eight were excluded from the final analysis due to intraoperative diagnosis of endometriosis; therefore, the remaining 12 patients were evaluated. The pain scores significantly decreased at each follow-up visit compared with the preoperative period (p=0.002). The pathologists, who were blinded, reported the median (minimum-maximum) neural fiber count as 46 (20-85) and 47 (18-83). No significant correlation was demonstrated between the number of excised neural fibers and the amount of pain relief following LPSN.
LPSN is an effective surgical procedure to control primary dysmenorrhea. Our preliminary results revealed that the degree of pain relief in cases of severe midline dysmenorrhea was not related to the amount of excised neural tissue in LPSN.
Am J Reprod Immunol. 2018 Mar;79(3). doi: 10.1111/aji.12817. Epub 2018 Jan 30.
Uterine natural killer cell progenitor populations predict successful implantation in women with endometriosis-associated infertility.
Uterine natural killer (uNK) cells play a critical role early in gestation. As we previously identified altered uNK cell development in endometriosis-associated infertility, we herein sought to characterize natural killer (NK) cell profiles in endometriosis that may predict embryo implantation.
METHOD OF STUDY:
Study participants had a surgical diagnosis of endometriosis-associated infertility. Endometrial tissue and peripheral blood were obtained from 58 women. Thirty-three patients underwent artificial reproductive technology (IVF, ICSI, or IUI) within a mean of 9.5 months of surgery. NK and hematopoietic progenitor cells from endometrium and blood were analyzed by flow cytometry. Successful implantation was defined as a positive pregnancy test.
In successful implantation, populations of endometrial CD34+ hematopoietic stem cells were higher (3.97% vs 0.69%; P < .0004), and coexpression of NK cell marker CD56 was increased (81.1% vs 60.9%; P < .034) compared with patients who had failed implantation. In contrast, levels of blood NK progenitors were similar in both groups.
Our study revealed that uterine NK progenitor cell populations are markedly different in patients with endometriosis who proceed to successful or failed embryo implantation and may define a novel predictor of implantation success. Our findings also highlight the fundamental differences inherent in NK cell repertoires between blood and uterine compartments.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Arch Gynecol Obstet. 2018 Apr;297(4):1005-1013. doi: 10.1007/s00404-018-4651-6. Epub 2018 Jan 30.
Is the presence of endometriosis associated with a survival benefit in pure ovarian clear cell carcinoma?
The purpose of this study was to compare the prognoses of women with pure ovarian clear cell carcinoma (OCCC) arising from endometriosis to those of women with pure OCCC not arising from endometriosis treated in the same manner.
A dual-institutional, retrospective database review was performed to identify patients with pure OCCC who were treated with maximal or optimal cytoreductive surgery (CRS) followed by paclitaxel/carboplatin chemotherapy between January 2006 and December 2016. Patients were divided into two groups according to the detection of cancer arising in endometriosis or not, on the basis of pathological findings. Demographic, clinicopathological, and survival data were collected, and prognosis was compared between the two groups.
Ninety-three women who met the inclusion criteria were included. Of these patients, 48 (51.6%) were diagnosed with OCCC arising in endometriosis, while 45 (48.4%) had no concomitant endometriosis. OCCC arising in endometriosis was found more frequently in younger women and had a higher incidence of early stage disease when compared to OCCC patients without endometriosis. The 5-year overall survival (OS) rate of the patients with OCCC arising in endometriosis was found to be significantly longer than that of women who had OCCC without endometriosis (74.1 vs. 46.4%; p = 0.003). Although univariate analysis revealed the absence of endometriosis (p = 0.003) as a prognostic factor for decreased OS, the extent of CRS was identified as an independent prognostic factor for both recurrence-free survival (hazard ratio (HR) 8.7, 95% confidence interval (CI) 3.15-24.38; p < 0.001) and OS (HR 11.7, 95% CI 3.68-33.71; p < 0.001) on multivariate analysis.
Our results suggest that endometriosis per se does not seem to affect the prognosis of pure OCCC.
Gynecol Endocrinol. 2018 Jan 31:1-5. doi: 10.1080/09513590.2018.1433160. [Epub ahead of print]
Heterogeneity of estrogen receptor α and progesterone receptor distribution in lesions of deep infiltrating endometriosis of untreated women or during exposure to various hormonal treatments.
Deep infiltrating endometriosis (DIE) responds variably to hormonal therapy. Mutations in cancer driver genes have been identified in a fraction of the ectopic endometrial epithelial cells, suggesting a functional heterogeneity of these lesions. To evaluate the phenotype heterogeneity of cells in DIE, we measured the expression of estrogen receptor α (ERα) and of progesterone receptor (PR) in DIE of untreated women or under various treatments. We analyzed the luminal epithelial height (LEH), immunoreactive epithelial staining (IRS) and stromal staining intensity (SSI) of ERα and PR. We observed a high variability in the same gland, among distinct glands in the same sample and among distinct patients receiving the same treatment. LEH variability was primarily due to epithelial cells heterogeneity in a gland, secondarily to the glands randomly evaluated on the same section, and tertiary to the patient category. Variability in IRS and SSI scores was primarily the consequence of their heterogeneity in the same woman and to a lesser extent to variability among patients. LEH and SSI were not modified according to treatment. IRS for PR was lower in treated patients. This heterogeneity of ERα and PR distribution could explain why endocrine treatments are unable to cure this condition.
Biol Reprod. 2018 Jan 29. doi: 10.1093/biolre/ioy019. [Epub ahead of print]
miRNA expression pattern differs depending on endometriosis lesion type.
MicroRNA (miRNA), non-coding segments of RNA involved in post-transcriptional regulation of protein expression, are differentially expressed in eutopic endometrium of women with and without endometriosis compared to endometriotic lesions. However, endometriotic lesion types are known to be biochemically distinct and therefore hypothesized that miRNAs are differentially expressed in endometriomas compared to peritoneal and deep-infiltrating lesions. Therefore endometrial biopsies and ectopic implants from women (n = 38) undergoing laparoscopic surgery for chronic pelvic pain were collected. Samples of endometriomas, peritoneal or deep infiltrating lesions were selected from our tissue bank for study participants who exclusively had only one lesion type noted on their surgical report. Quantitative real-time polymerase chain reaction (qPCR) for miR-9, miR-21, miR-424, miR-10a, miR-10b, and miR-204 was performed. miR-204 expression was significantly lower (p = 0.0016) in the eutopic endometrium of women with endometriosis compared to controls. Relative expression of miR-21, miR-424, and miR-10b differed significantly (p < 0.05) across endometriotic lesion types. Finally, all miRNAs isolated from endometriomas, peritoneal, and deep infiltrating lesions studied were differentially expressed compared to matched eutopic endometrium samples. We therefore conclude that miRNA expression in the eutopic endometrium from women with endometriosis differs from symptomatic controls. Moreover, miRNA expression pattern is dependent on the endometriotic lesion type studied. We suggest that identification of different miRNA expression patterns for endometriomas, peritoneal and deep-infiltrating lesions could contribute to individualized patient care for women with endometriosis.
BMC Med Genet. 2018 Jan 31;19(1):20. doi: 10.1186/s12881-018-0537-5.
Whole exome sequencing of benign pulmonary metastasizing leiomyoma reveals mutation in the BMP8B gene.
Benign metastasizing leiomyoma (BML) is an orphan neoplasm commonly characterized by pulmonary metastases consisting of smooth muscle cells. Patients with BML have usually a current or previous uterine leiomyoma, which is therefore suggested to be the most probable source of this tumour. The purpose of this case report was to determine the possible genetic grounds for pulmonary BML.
We present a case report in an asymptomatic 44-year-old female patient, who has developed uterine leiomyoma with subsequent pulmonary BML. Whole exome sequencing (WES) was used to detect somatic mutations in BML lesion. Somatic single nucleotide mutations were identified by comparing the WES data between the pulmonary metastasis and blood sample of the same BML patient. One heterozygous somatic mutation was selected for validation by Sanger sequencing. Clonality of the pulmonary metastasis and uterine leiomyoma was assessed by X-chromosome inactivation assay.
We describe a potentially deleterious somatic heterozygous mutation in bone morphogenetic protein 8B (BMP8B) gene (c.1139A > G, Tyr380Cys) that was identified in the pulmonary metastasis and was absent from blood and uterine leiomyoma, and may play a facilitating role in the metastasizing of BML. The clonality assay confirmed a skewed pattern of X-chromosome inactivation, suggesting monoclonal origin of the pulmonary metastases.
Exp Ther Med. 2018 Jan;15(1):479-486. doi: 10.3892/etm.2017.5390. Epub 2017 Oct 30.
Advanced oxidation protein products from the follicular microenvironment and their role in infertile women with endometriosis.
Endometriosis (EM) is associated with oxidative stress. Advanced oxidation protein products (AOPPs) are novel markers of oxidative stress, which serve an important role as an inflammatory mediator in various chronic diseases. In order to examine the role of AOPPs in infertile women with EM, the present study analyzed the levels of AOPPs, estradiol (E2) and progesterone (P4) in the follicular fluid (FF) of 89 women with or without EM undergoing in vitro fertilization (IVF). The AOPP concentration in the FF of the EM group was significantly higher when compared with that of the control group (51.5±22.4 vs. 41.8±18.3 µmol/l; P<0.05). However, the FF P4 levels and blastocyst rate were significantly lower in the EM group compared with the control group (P4:1,249.6±465.4 vs. 1,752.7±565.4 ng/ml, P<0.05; blastocyst rate: 0.511±0.322 vs. 0.662±0.278; P<0.05). The AOPP concentration and P4 level in the FF presented a significant negative correlation in the EM and control groups, as well as in the total cohort of patients (EM group: r=-0.406, P=0.006; control group: r=-0.315, P=0.035; total: r=-0.421, P<0.001). In addition, there was a significant negative correlation between the FF AOPP concentrations and blastocyst rate in the EM group and in the total cohort (EM group: r=-0.376, P=0.012; total: r=-0.367, P<0.001). In conclusion, these results suggested that AOPPs may be a potentially effective marker for predicting the oocyte quality and outcomes of IVF in infertile women with EM.
Skin Res Technol. 2018 Jan 31. doi: 10.1111/srt.12431. [Epub ahead of print]
New findings in non-invasive imaging of cutaneous endometriosis: Dermoscopy, high-frequency ultrasound and reflectance confocal microscopy.
Cutaneous endometriosis (CE) is rare and its dermoscopic features were reported only in 3 patients. The aim of this study was to examine a case of pigmented CE with multiple non-invasive imaging techniques, to compare the obtained images with histopathology and to define their utility in an early diagnosis of the disease.
We performed dermoscopy, high-frequency ultrasound (HFUS), in vivo and ex vivo reflectance confocal microscopy (RCM) of a pigmented CE arising on the caesarean scar of a phototype IV patient, along with histologic studies. Dermoscopy showed a greyish background and a brownish pigmentation. HFUS shows well-demarcated anechoic areas corresponding to ectopic endometrial tissue at histopathologic examination. RCM and OCT only showed the alterations of the epidermis.
High-frequency ultrasound could represent a very useful tool for an early diagnosis of CE and its usefulness could be tested in patients with unusual cyclical pain, even before skin lesion appearance. RCM allowed the visualization of skin surface modification due to underlying endometriosic tissue. Dermoscopy showed a new aspect that was probably related to the mix of blood extravasation (ie, greyish background) and epidermal pigmentation (ie, brown pigmentation).
Endocr Rev. 2018 Jan 30. doi: 10.1210/er.2017-00229. [Epub ahead of print]
Extracellular Vesicles in Human Reproduction in Health and Disease.
Extensive evidence suggests that the release of membrane enclosed compartments, more commonly known as extracellular vesicles (EVs), is a potent newly identified mechanism of cell-to-cell communication both in normal physiology and in pathological conditions. This article specifically reviews evidence about the formation and release of different EVs, their definitive markers and cargo content in reproductive physiological processes, and their capacity to convey information between cells through the transfer of functional protein and genetic information to alter phenotype and function of recipient cells associated with reproductive biology. In the male reproductive tract, epididymosomes and prostasomes participate in regulating sperm motility activation, capacitation and acrosome reaction. In the female reproductive tract, follicular fluid, oviduct/tube and uterine cavity EVs are considered as vehicles to carry information during oocyte maturation, fertilization and embryo-maternal cross talk. EVs via their cargo might be also involved in the triggering, maintenance and progression of reproductive and obstetric related pathologies such as endometriosis, polycystic ovarian syndrome, pre-eclampsia, gestational diabetes, and erectile disfunction. We provide here, the current knowledge on the present and future use of EVs not only as biomarkers, but also as therapeutic targeting agents, mainly as vectors for drug/compounds delivery into target cells/tissues.
Aktuelle Urol. 2018 Feb;49(1):60-72. doi: 10.1055/s-0043-122175. Epub 2018 Feb 1.
Combined treatment of endometriosis: radical yet gentle.
Endometriosis is the second most common benign female genital disease after uterine myoma. This review discusses the management of individual patients. This should take into account the severity of the disease and whether the patient desires to have children. Particular emphasis is laid on the anatomical intersections which, when injured, can lead to persistent damage of the anterior, middle or posterior compartment and are not infrequently the cause of urological and urogynaecological follow-up measures. Typical symptoms of endometriosis include chronic pelvic pain, subfertility, dysmenorrhoea, deep dyspareunia, cyclical bowel or bladder symptoms (e. g. dyschezia, bloating, constipation, rectal bleeding, diarrhoea and haematuria), abnormal menstrual bleeding, chronic fatigue and low back pain. Approx. 50 % of all female teenagers and up to 32 % of all women of reproductive age who have been operated for chronic pelvic pain or dysmenorrhoea suffer from endometriosis. The time interval between the first unspecific symptoms and the medical diagnosis of endometriosis is about 7 years. This is caused not only by the non-specific nature of the symptoms but also by the frequent lack of awareness on the part of the cooperating disciplines with which the patients have first contact. As the pathogenesis of endometriosis is not clearly understood, causal treatment is still impossible. Treatment options include expectant management, analgesia, hormonal medical therapy, surgical intervention and the combination of medical treatment before and/or after surgery. The treatment should be as radical as necessary and as minimal as possible. The recurrence rate among treated patients lies between 5 % and > 60 % and is very much dependent on integrated management and surgical skills. Consequently, to optimise the individual patient’s treatment, a high degree of interdisciplinary cooperation in diagnosis and treatment is crucial and should be reserved to appropriate centres - especially in the case of deep infiltrating endometriosis.
J Obstet Gynaecol. 2018 Feb 1:1-7. doi: 10.1080/01443615.2017.1374933. [Epub ahead of print]
Comparison of the symptoms and localisation of endometriosis involvement according to fertility status of endometriosis patients.
This cross-sectional study aimed to assess the prevalence of endometriosis in women who were referred for Diagnostic Laparoscopy Unit due to infertility or pelvic pain between January 2012 and January 2013 and compare the symptoms and laparoscopic signs among the three groups according to the fertility status. Four hundred and thirteen women were evaluated; of these, 383 patients for infertility and 30 patients for pelvic pain and/or cyst. Endometriosis symptoms were compared between fertile and infertile women with primary and secondary infertility. There was no statistically significant difference in the overall prevalence of endometriosis between the three study groups (52.9%, 45% and 40.7%, respectively, in primary, secondary infertile and fertile women). The endometriosis stage was categorised as early- (I and II) or late- (III and IV) stages and the extent of endometriosis was divided into peritoneal, ovarian and ovarian coexisting with peritoneal. There is no relationship between the frequency of dysmenorrhoea or non-cyclic pelvic pain and the disease stage; although these pain symptoms are significantly more prevalent in cases with both ovarian and peritoneal endometriotic implants. Infertility was more prevalent among the patients with peritoneal endometriosis in comparison to the ones with ovarian endometriosis. Further studies with a larger sample size are required to confirm these findings. Impact statement What is already known on this subject? Few studies have been done in this area and only one study compared the localisation of endometriosis lesions between fertile and infertile endometriosis cases; however, more study is needed to confirm their results. What the results of this study add? A possible relationship between localisation of endometriosis involvement and infertility was found in the present study in agreement to result of a previous study performance in this area. Although the present study includes a greater number of cases than that of the previous reported study, further studies with a larger sample size are required for the confirmation or refusal of this finding. What are the implications of these findings for clinical practice and/or further research? The results of this study could have clinical application in the consultation and decision-making in infertile women with an endometriosis diagnosis.
Reprod Biol Endocrinol. 2018 Feb 1;16(1):9. doi: 10.1186/s12958-018-0325-2.
Suppressive regulatory T cells and latent transforming growth factor-β-expressing macrophages are altered in the peritoneal fluid of patients with endometriosis.
Endometriosis is a known cause of infertility. Differences in immune tolerance caused by regulatory T cells (Tregs) and transforming growth factor-β (TGF-β) are thought to be involved in the pathology of endometriosis. Evidence has indicated that Tregs can be separated into three functionally and phenotypically distinct subpopulations and that activated TGF-β is released from latency-associated peptide (LAP) on the surfaces of specific cells. The aim of this study was to examine differences in Treg subpopulations and LAP in the peripheral blood (PB) and peritoneal fluid (PF) of patients with and without endometriosis.
PB and PF were collected from 28 women with laparoscopically and histopathologically diagnosed endometriosis and 20 disease-free women who were subjected to laparoscopic surgery. Three subpopulations of CD4+ T lymphocytes (CD45RA+FoxP3low resting Tregs, CD45RA–FoxP3high effector Tregs, and CD45RA–FoxP3low non-Tregs) and CD11b+mononuclear cells expressing LAP were analyzed by flow cytometry using specific monoclonal antibodies.
Proportions of suppressive Tregs (resting and effector Tregs) were significantly higher in the PF samples of patients with endometriosis than in those of control women (P = 0.02 and P < 0.01, respectively) but did not differ between the PB samples of patients and controls. The percentage of CD11b+LAP+ macrophages was significantly lower in PF samples of patients with endometriosis than in those of controls (P < 0.01) but was not altered in the PB samples.
Proportions of suppressive Tregs and LAP+ macrophages are altered locally in the PF of endometriosis patients.
J Gynecol Obstet Hum Reprod. 2018 Jan 31.
Ureteral obstruction and ruptured kidney following ovarian hyperstimulation syndrome.
In vitro fertilization (IVF) is nowadays a reliable and common method for couple who need medically assisted procreation. Complications are rare. We report in this paper, the case of a woman with severe endometriosis who developed ureteral obstruction complicated by a renal rupture of the fornix due to ovarian hyperstimulation during an IVF attempt. The condition was diagnosed by CT scan and resolved with insertion of double-J catheter in the left ureter.
Mol Imaging Radionucl Ther. 2018 Feb 1;27(1):52-54. doi: 10.4274/mirt.77044.
Inguinal Endometriosis Visualized on I-131 Whole Body Scan.
We present a rare case with inguinal iodine-131 (I-131) uptake on whole body scan. The patient was suffering from a painful right inguinal mass during menstrual period, which was later sonographically and histopathologically confirmed to be an inguinal focus of endometriosis. Endometriosis is a previously reported site of radioiodine uptake and detection of radioiodine uptake in the inguinal region has also been described. Nevertheless, to the best of our knowledge, this is the first case report of I-131 uptake in an inguinal endometriosis focus. History and physical examination of the patient are both very important in identifying the etiology of the ectopic uptake sites on I-131 whole body scan, and inguinal endometriosis should be kept in mind while reporting inguinal radioiodine uptake on I-131 whole body scan.
Mol Med Rep. 2018 Apr;17(4):5435-5439. doi: 10.3892/mmr.2018.8510. Epub 2018 Jan 26.
Novel TRERF1 mutations in Chinese patients with ovarian endometriosis.
Endometriosis is an estrogen-dependent precancerous lesion exhibiting frequently perturbed level of steroid hormones and transcriptional‑regulating factor 1 (TRERF1) has a crucial role in the production of steroid hormones including estrogen. Endometriosis has previously been revealed to be a precancerous lesion that harbors somatic mutations in cancer‑associated genes. Therefore, the authors of the present study hypothesize that TRERF1 aberrations may be involved in the development of endometriosis. In the present study, endometriotic lesions and paired blood samples from 92 individuals with ovarian endometriosis were analyzed for the potential presence of TRERF1 mutations by sequencing the entire coding region and the corresponding intron‑exon boundaries of the TRERF1 gene. Two heterozygous missense somatic mutations [c.3166A>C (p.K1056Q) and c.3187 G>A (p.G1063R)] in the TRERF1 gene were identified in two out of 92 ectopic endometria (2.2%), to the best of our knowledge, these mutations have not been previously reported. From the two samples with TRERF1 mutations, one sample was from a 42‑year‑old patient also diagnosed with uterine leiomyoma and the other mutation was identified in a 36‑year‑old woman exhibiting no other apparent gynecological conditions. The evolutionary conservation analysis and in silico prediction of these TRERF1 mutations suggested that they may be pathogenic. To the best of our knowledge, the present study was the first to identify 2 novel, potentially ‘disease‑causing’ TRERF1 somatic mutations in the endometriotic lesions in 2 out of 92 patients with ovarian endometriosis; therefore, TRERF1 mutations may be involved in the pathogenesis of ovarian endometriosis.
Dig Liver Dis. 2018 Mar;50(3):213-219. doi: 10.1016/j.dld.2017.12.017. Epub 2017 Dec 27.
Irritable bowel syndrome and endometriosis: New insights for old diseases.
Irritable bowel syndrome and endometriosis are two diseases affecting a significant part of the female population, either together or individually, with remarkable consequences in the quality of life. Several studies suggest an epidemiological association between them. Their association may not be just an epidemiological phenomenon, but the manifestation of a pathophysiological correlation, which probably generates a mutual promotion phenomenon. In particular, both clinical entities share the presence of a chronic low-grade inflammatory state at the basis of the disease persistence. Recognizing this association is highly significant due to their prevalence and the common clinical manifestation occurring with a chronic abdominal pain. A further multi disciplinary approach is suggested in these patients’ management in order to achieve an adequate diagnostic work up and a targeted therapy. This paper analyses some common pathophysiological mechanisms, such as activation of mast cell line, neuronal inflammation, dysbiosis and impaired intestinal permeability. The aim was to investigate their presence in both IBS and endometriosis, and to show the complexity of their relationship in the generation and maintenance of chronic inflammation.
Cell Immunol. 2018 Jan 9.
The biology of serous cavity macrophages.
For decades, it has been known that the serous cavities, which include the peritoneal, pleural and pericardial cavities, harbour large numbers of macrophages. In particular, due to the ease of isolating these cells, the peritoneal cavity has been used as a convenient source of macrophages to examine many facets of macrophage biology over the last 50-60 years. Despite this, it is only recently that the true heterogeneity of serous cavity mononuclear phagocyte compartment, which includes macrophages and dendritic cells, has been revealed. Advances in technologies such as multi-parameter flow cytometry and the ‘OMICs’ revolution have uncovered the presence of distinct populations of mononuclear phagocytes in the serous cavities. Given that peritoneal macrophages have been implicated in many pathologies, including peritonitis, pancreatitis, endometriosis and acute liver injury, it is imperative to understand the biology of these cells. Here, we review the recent advances in understanding the identity, origin and function of discrete serous cavity mononuclear phagocyte subsets in homeostasis and how these may change when homeostasis is perturbed, focusing on peritoneal and pleural cavities and highlighting differences in the mononuclear phagocytes found in each.
Fertil Steril. 2018 Feb 1. pii: S0015-0282(17)32171-4.
Dehydroepiandrosterone enhances decidualization in women of advanced reproductive age.
To investigate the impact of the androgen precursor dehydroepiandrosterone (DHEA) on the decidualization of human endometrial stromal cells isolated from women of advanced reproductive age.
In vitro study.
University research institute.
Proliferative phase primary human endometrial stromal fibroblasts (hESFs) were isolated from women of advanced reproductive age (n = 16; mean age, 44.7 ± 2.3). None of the women were receiving hormone therapy or had endometriosis.
Isolated hESFs were decidualized in vitro by incubation with P (1 μM) and cAMP (0.1 mg/mL) in the presence, or absence, of DHEA (10 nM, 100 nM).
MAIN OUTCOME MEASURE(S):
Secretion of androgens was assessed by ELISA. Expression of decidualization markers and endometrial receptivity markers was assessed by quantitative polymerase chain reaction and ELISA.
Decidualization responses were retained in hESF isolated from women of advanced reproductive age. Supplementation with DHEA increased androgen biosynthesis and concentrations of T and dihydrotestosterone were ∼3× greater after coincubation with DHEA compared with hESF stimulated with decidualization alone. Addition of DHEA to decidualized hESF increased expression of the decidualization markers IGFBP1 and PRL and the endometrial receptivity marker SPP1. DHEA enhanced secretion of IGFBP1, PRL, and SPP1 proteins maximally by day 8 of the decidualization time course concomitant with peak androgen concentrations.
These novel results demonstrate DHEA can enhance in vitro decidualization responses of hESF from women of advanced reproductive age. Supplementation with DHEA during the receptive phase may augment endometrial function and improve pregnancy rates in natural or assisted reproductive cycles.
Reprod Biomed Online. 2018 Mar;36(3):294-301. doi: 10.1016/j.rbmo.2017.11.010. Epub 2017 Dec 28.
The endometrial stem cell markers notch-1 and numb are associated with endometriosis.
Previous studies reported increased expression of the notch pathway-associated protein Musashi-1 in endometriosis. This case-control study investigates an association of the endometrial stem cell markers notch-1 and numb with endometriosis. Fifty-one endometriosis patients and 76 controls were recruited in the IVF unit and tertiary endometriosis referral centre of a university hospital. All subjects underwent transcervical endometrial biopsy and diagnostic laparoscopy. Expression of endometrial notch-1 and numb was assessed by immunostaining and correlated with clinical data. Association of stem-cell-marker expression with the presence of endometriosis was evaluated. Numb expression in the luminal epithelium was significantly higher in eutopic endometrium of endometriosis patients compared with controls (20.5% versus 16.5%, P = 0.033). Numb-positive single stromal cells were less frequent in endometrioma patients compared with other forms of endometriosis (0.3 versus 0.5 cells/visual field; P = 0.028). Notch-1 expression in endometrial glands was significantly higher in patients with deep infiltrating endometriosiscompared with controls (39.1% versus 21.8%; P = 0.045). We conclude that stem cell markers notch-1 and numb of eutopic endometrium are associated with endometriosis and its clinical presentations, supporting the stem cell hypothesis of endometriosis. These findings could help develop promising research strategies applying endometrial stem cells as novel tools.
J Gynecol Oncol. 2018 Mar;29(2):e18. doi: 10.3802/jgo.2018.29.e18. Epub 2017 Dec 11.
Clinical outcomes of patients with clear cell and endometrioid ovarian cancer arising from endometriosis.
The aim of this investigation is to compare outcomes of patients according to the presence of cancer arising from endometriosis in ovarian clear cell carcinoma (CCC) and endometrioid carcinoma (EC).
This study retrospectively investigated 224 CCC and EC patients treated in Samsung Medical Center from 2001 to 2015 to identify cancer arising from endometriosis according to Sampson and Scott criteria. Propensity score matching was performed to compare patients arising from endometriosis to patients without endometriosis (ratio 1:1) according to stage, age, lymph node metastasis (LNM), cancer antigen (CA)-125 level, and residual status after debulking surgery.
Forty-five cases arising from endometriosis were compared with 179 cases without endometriosis. CCC and EC arising from endometriosis tended to present with early age (mean, 45.2 vs. 49.2 years; p=0.003), early-stage (stages I and II, 92.7% vs. 62.3%; p<0.001), lower CA-125 level (mean, 307.1 vs. 556.7; p=0.041), higher percentages of no gross residual disease after surgery (87.8% vs.56.8%; p=0.001), and higher percentages of negative LNM (82.9% vs. 59.0%; p=0.008) compared to cases without endometriosis. Kaplan-Meier curves for progression-free survival (PFS) and overall survival (OS) showed better outcomes for groups with cancer arising from endometriosis (p=0.014 for PFS; and p=0.010 for OS). However, the association with endometriosis was not significant in multivariate analysis. Also, after propensity score matching, survival differences between the 2 groups were not significant.
CCC and EC arising from endometriosis are diagnosed at an earlier age and stage. However, cancer arising from endometriosis was not a significant prognostic factor.
J Gynecol Oncol. 2018 Feb 1.
Risk factors in progression from endometriosis to ovarian cancer: a cohort study based on medical insurance data.
The objective was to identify risk factors that were associated with the progression from endometriosis to ovarian cancer based on medical insurance data.
The study was performed on a dataset obtained from the National Health Insurance Research Database, which covered all the inpatient claim data from 2000 to 2013 in Taiwan. The International Classification of Diseases (ICD) code 617 was used to screen the dataset for the patients who were admitted to hospital due to endometriosis. They were then tracked for subsequent diagnosis of ovarian cancer, and available biological, socioeconomic and clinical information was also collected. Univariate and multivariate analyses were then performed based on the Cox regression model to identify risk factors. C-index was calculated and cross validated.
A total of 229,617 patients who were admitted to hospital due to endometriosis from 2000 to 2013 were included in the study, out of whom 1,473 developed ovarian cancer by the end of 2013. A variety of factors, including age, residence, hospital stratification, premium range, and various comorbidities had significant impact on the progression (p<0.05). Among them, age, urbanization of residence, hospital stratification, premium range, post-endometriosis childbearing, pelvic inflammation, and depression all had independent, significant impact (p<0.05). The validated C-index was 0.69.
For a woman diagnosed with endometriosis, increased age, residing in a highly urbanized area, low or high income, depression, pelvic inflammation, and absence of childbearing post-endometriosis all put her at high-risk to develop ovarian cancer. The findings may be of help to gynecologists to identify high-risk patients.
J Obstet Gynaecol Res. 2018 Feb 5. doi: 10.1111/jog.13595. [Epub ahead of print]
Endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy: A case report.
Malignant transformation of diaphragmatic endometriosis is rare. We present a case of endometrioid carcinoma arising from diaphragmatic endometriosis treated with laparoscopy. A 59-year-old primigravida woman who had undergone abdominal hysterectomy for adenomyosis at the age of 47 years was referred to our hospital for investigation of a tumor on the surface of the liver. An integrated positron emission tomography-computed tomography scan revealed a 3-cm nodule on the surface of the liver with abnormal fluorine-18-deoxyglucose accumulation. Partial resection of the diaphragm and liver was performed. Histopathological examination revealed an endometrioid carcinoma arising from diaphragmatic endometriosis. We additionally performed laparoscopic bilateral salpingo-oophorectomy and partial omentectomy. The resected tissues revealed no malignancy. Adjuvant chemotherapy with paclitaxel and carboplatin was administered. In cases of diaphragmatic tumors, endometriosis and its associated malignancies should be considered. Laparoscopic surgery is effective in patients with such conditions.
Hum Reprod. 2018 Feb 1.
Fruit and vegetable consumption and risk of endometriosis.
Is there an association between intake of fruits and vegetables and risk of laparoscopically confirmed endometriosis?
Higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis.
WHAT IS KNOWN ALREADY:
Two case-control studies have examined the associations between fruit and vegetable intake and endometriosis risk with contrasting results. Diets rich in fruits and vegetables include higher levels of pro-vitamin A nutrients (alpha-carotene, beta-carotene, beta-cryptoxanthin) and women with endometriosis have been reported to have lower intake of vitamin A than women without endometriosis.
STUDY DESIGN SIZE, DURATION:
A prospective cohort study using data collected from 70 835 premenopausal women from 1991 to 2013 as part of the Nurses’ Health Study II cohort.
PARTICIPANTS/MATERIALS, SETTING, METHODS:
Diet was assessed with a validated food frequency questionnaire (FFQ) every 4 years. Cases were restricted to laparoscopically confirmed endometriosis. Cox proportional hazards models were used to calculate rate ratios (RR) and 95% CI.
MAIN RESULTS AND THE ROLE OF CHANCE:
During 840 012 person-years of follow-up, 2609 incident cases of laparoscopically confirmed endometriosis were reported (incidence rate = 311 per 100 000 person-years). We observed a non-linear inverse association between higher fruit consumption and risk of laparoscopically confirmed endometriosis (Psignificance of the curve = 0.005). This inverse association was particularly evident for citrus fruits. Women consuming ≥1 servings of citrus fruits/day had a 22% lower endometriosis risk (95% CI = 0.69-0.89; Ptrend = 0.004) compared to those consuming <1 serving/week. No association was observed between total vegetable intake and endometriosis risk. However, women consuming ≥1 servings/day cruciferous vegetables had a 13% higher risk of endometriosis (95% CI = 0.95-1.34; Ptrend = 0.03) compared to those consuming <1 serving/week. Of the nutrients examined, only beta-cryptoxanthin intake was significantly associated with lower endometriosis risk (RR fifth quintile = 0.88; 95% CI = 0.78-1.00; Ptrend = 0.02).
LIMITATIONS REASONS FOR CAUTION:
Some error in the self-reporting of dietary intake is expected, however, use of a validated FFQ and examining diet prospectively across multiple time points, make it unlikely that this non-differential misclassification strongly influenced the results.
WIDER IMPLICATIONS OF THE FINDINGS:
Our findings suggest that a higher intake of fruits, particularly citrus fruits, is associated with a lower risk of endometriosis, and beta-cryptoxanthin in these foods may partially explain this association. In contrast to what we hypothesized, consumption of some vegetables increased endometriosis risk which may indicate a role of gastrointestinal symptoms in both the presentation and exacerbation of endometriosis-related pain; however, it is not clear what components of these foods might underlie the observed associations. Future studies examining dietary patterns that consider different combinations of food intake may help clarify these associations.
STUDY FUNDING/COMPETING INTEREST(S):
This work was supported by research grants HD4854, HD52473 and HD57210 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and grant P30 DK046200 from the National Institute of Diabetes and Digestive and Kidney Diseases. The Nurses’ Health Study II is supported by the Public Health Service grant UM1 CA176726 from the National Cancer Institute, National Institutes of Health. HRH is supported by the National Cancer Institute, National Institutes of Health (K22 CA193860). No competing interests.
TRIAL REGISTRATION NUMBER:
© The Author(s) 2018. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology.
Reprod Sci. 2018 Jan 1:1933719118756751.
The Essential Role of GATA6 in the Activation of Estrogen Synthesis in Endometriosis.
Endometriotic stromal cells synthesize estradiol via the steroidogenic pathway. Nuclear receptor subfamily 5, group A, member 1 (NR5A1) is critical, but alone not sufficient, in activating this cascade that involves at least 5 genes. To evaluate whether another transcription factor is required for the activation of this pathway, we examined whether GATA Binding Protein 6 (GATA6) can transform a normal endometrial stromal cell (NoEM) into an endometriotic-like cell by conferring an estrogen-producing phenotype. We ectopically expressed GATA6 alone or with NR5A1 in NoEM or silenced these transcription factors in endometriotic stromal cells (OSIS) and assessed the messenger RNAs or proteins encoded by the genes in the steroidogenic cascade. Functionally, we assessed the effects of GATA6 expression or silencing on estradiol formation. In OSIS, GATA6 was necessary for catalyzing the conversion of progesterone to androstenedione (CYP17A1; P < .05). In NoEM, ectopic expression of GATA6 was essential for converting pregnenolone to estrogen (HSD3B2, CYP17A1, and CYP19A1; P < .05). However, simultaneous ectopic expression of both GATA6 and NR5A1 was required and sufficient to confer induction of all 5 genes and their encoded proteins that convert cholesterol to estrogen. Functionally, only simultaneous knockdown of GATA6 and NR5A1 blocked estradiol formation in OSIS ( P < .05). The presence of both transcription factors was required and sufficient to transform endometrial stromal cells into endometriotic-like cells that produced estradiol in large quantities ( P < .05). In summary, GATA6 alone is essential but not sufficient for estrogen formation in endometriosis. However, simultaneous addition of GATA6 and NR5A1 to an endometrial stromal cell is sufficient to transform it into an endometriotic-like cell, manifested by the activation of the estradiol biosynthetic cascade.
Reprod Sci. 2018 Apr;25(4):480-486. doi: 10.1177/1933719118756754. Epub 2018 Feb 5.
Fertility-Sparing Treatment of Adenomyosis in Patients With Infertility: A Systematic Review of Current Options.
Adenomyosis is a benign gynecological disease observed in women in their reproductive age. Recent studies have shown that adenomyosis might be a relevant factor for infertility, either impairing implantation or leading to early miscarriage. However, conservative treatment of infertility related to adenomyosis is still unclear. This study systematically reviews the literature for the reproductive outcomes of the available conservative treatments for patients with adenomyosis-associated infertility. We conducted a search in PubMed/Medline for studies in English published in the last 7 years and included 16 studies. Six studies evaluated surgical treatments of adenomyosis. When considering only spontaneous pregnancies, the overall clinical pregnancy rate was very low (18.2%). However, when using GnRH analogues for 24 weeks after surgery, the pooled spontaneous pregnancy rate was higher (40.7% vs 15.0%; P = .002). No significant difference was observed in the other outcomes. Ten studies evaluated exclusive assisted reproductive techniques for infertility related to adenomyosis and showed that the long stimulation protocol had better outcomes compared to short stimulation protocol in pregnancy rate (43.3% vs 31.8%; P = .0001), live birth (43.0% vs 23.1%; P = .005), and miscarriage (18.5% vs 31.1%; P < .0001).
Reprod Sci. 2018 Jan 1:1933719118756745. doi: 10.1177/1933719118756745. [Epub ahead of print]
Similar Characteristics of Endometrial and Endometriotic Epithelial Cells.
Epithelial-mesenchymal transition (EMT) is characterized by the loss of epithelial and acquisition of mesenchymal cell characteristics. Our aim was to assess the epithelial phenotype in the pathogenesis of endometriosis with epithelial and mesenchymal markers. We used 2 structural (keratin-18, -19 [K18, K19]), 1 membrane-associated (mucin-1 [MUC1]), and 2 mesenchymal proteins (vimentin; zinc finger E-box-binding homeobox 1, [ZEB1]) to compare epithelial and mesenchymal characteristics in eutopic endometrium with the 3 endometriotic entities, peritoneal, ovarian, and deep infiltrating endometriosis(DIE). Quantitation showed no differences for K18, K19, and MUC1 between endometrium with and without endometriosis. Also, K18 was not different between endometrium and endometriotic lesions. In contrast, K19 and MUC1 were modestly but significantly decreased in the endometriotic lesions compared to endometrium. However, the maintained expression of epithelial markers in all investigated tissues, regardless of the pathological condition, clearly indicates no loss of the epithelial phenotype. This is further supported by the reduced presence of epithelial vimentin in endometriotic lesions which is in contrast to an increase in stromal vimentin in ectopic endometrium, especially in ovarian endometriosis. The ZEB1 increase in endometriotic lesions, especially in DIE, on the other hand suggests a role of partial EMT in the development of endometriotic lesions, possibly connected with the gain of invasive capabilities or stemness. Taken together, although we found some hints for at least a partial EMT, we did not observe a severe loss of the epithelial cell phenotype. Thus, we propose that EMT is not a main factor in the pathogenesis of endometriosis.
BMC Cancer. 2018 Feb 5;18(1):134. doi: 10.1186/s12885-018-4037-y.
Primary extra-uterine and extra-ovarian mullerian adenosarcoma: case report and literature review.
Extra-uterine mullerian adenosarcomas have varying biological behaviours depending on the presence of endometriosis or sarcomatous overgrowth. These behaviours manifest according to the tumours’ histological characteristics and sites of origin. The best treatment and oncologic outcome have not been clarified because only a few cases of extra-uterine and extra-ovarian adenosarcoma have been described in the literature. Here, we report a case of primary peritoneal adenosarcoma with sarcomatous overgrowth and review all reported cases of adenosarcomas arising outside of the uterus and outside the ovaries to identify the best treatment options and clarify outcomes.
A 79-year-old woman was referred to our Department with an abdominal mass resembling a fibroid with a haemorrhage. Her gynaecological history was negative. A transvaginal and transabdominal ultrasound examination revealed a multicystic mass resembling an ovarian tumour arising from the pelvis and extending up to the abdomen. At laparotomy a peritoneal mass arising from Douglas peritoneum was resected. The uterus and adnexa appeared normal, and a supra-cervical hysterectomy with bilateral salpingo-oophorectomy was performed. No macroscopic residual disease was present. Final pathology diagnosed a malignant peripheral nerve sheath tumors with divergent differentiation. Four weeks later a new, multicystic mass was found. Due to the progressive poor condition, the patient died four months after diagnosis. Histological slides were reviewed by external expert pathologists and the final diagnosis was of extra-genital adenosarcoma with sarcomatous overgrowth. Furthermore, we also collected and analysed articles written in English regarding extra-uterine and extra-ovarian adenosarcomas published between January 1974 and October 2016. PubMed was used as a database for this search. Clinical and pathological characteristics, treatments and outcomes were assessed.
Only 41 cases has been reported in literature. Previous endometriosis and sarcomatous overgrowth showed an inverse effect on prognosis. Endometriosis was confirmed to have a positive effect on disease free survival Complete surgical resection is the mainstay of treatment. A worldwide registry is urgently required to collect data to standardize treatment and to obtain reliable data on prognosis.
Eur J Obstet Gynecol Reprod Biol. 2018 Mar;222:119-125. doi: 10.1016/j.ejogrb.2018.01.025. Epub 2018 Feb 3.
Role of Lh polymorphisms and r-hLh supplementation in GnRh agonist treated ART cycles: A cross sectional study.
To investigate the effect of N312S polymorphism in the LHCGR gene as a predictive pharmacogenetic marker on clinical and embryological parameters and determining the need of r-hLH supplementation combine with r-hFSH in patients undergoing ART treatment.
In a cross-sectional study, a retrospective analysis of women (n = 553), who underwent controlled ovarian stimulation treatment protocol was conducted during the years 2012-2014. R-hFSH (Gonal-F, Merck Serono) was administered to all patients undergoing ART cycle after initiating long luteal gonadotrophin-releasing hormone (GnRH) agonist down-regulation. R-hLH was supplemented based on P.C. Wong criteria. N312S genotype was determined using sequencing methodology. The mean r-hFSH, r-hLH doses, total number of oocytes, cleavage rates of embryos and clinical pregnancy were recorded. The association between the r-hLH supplementation and LHCGR N312S polymorphism and clinical pregnancy rates was determined using regression analysis by SPSS.
19.7% of women were homozygous for A allele encoding asparagine (N/N), 45.7% were heterozygous (N/S) and 34.6% were homozygous (S/S) for G allele encoding serine. Women heterozygous (N/S) or homozygous (S/S) for serine showed a higher requirement for r-hLH (OR, 95% p-trend = <0.0001) compared to those homozygous for asparagine (N/N). Homozygous G allele was also associated with higher daily and total r-hLH dose per treatment cycle p-trend = <0.0001. Though, the total no of oocytes (14.87 ± 4.95 vs 12.98 ± 5.39 and 13.58 ± 5.45), Gr-I quality embryos (2.61 ± 1.81 vs 2.18 ± 1.96 and 1.98 ± 2.05) were significantly higher in women homozygous for A allele compared to women with heterozygous and homozygous for G allele, clinical pregnancy rates were significantly more in women with for G allele after excluding patients with PCOS and endometriosisconditions (P < 0.04).
The present findings reveal that women heterozygous and homozygous for G allele required higher doses of r-hLH supplementation and these women were shown to have higher clinical pregnancy rates.
Eur J Obstet Gynecol Reprod Biol. 2018 Mar;222:89-94. doi: 10.1016/j.ejogrb.2018.01.022. Epub 2018 Feb 3.
Norethindrone acetate versus extended-cycle oral contraceptive (Seasonique®) in the treatment of endometriosis symptoms: A prospective open-label comparative study.
This patient preference prospective study was designed to compare patients’ satisfaction in women with endometriosis treated either by an extended-cycle oral contraception (OC) or by norethindrone acetate (NETA).
This patient preference prospective study included women of reproductive age with endometriosis. Patients were submitted to one of the following 12 months’ treatments: Group A, continuous oral treatment with NETA (2.5 mg/day) and Group B, a 91-day extended-cycle OC (LNG/EE 150/30 mcg for 84 days and EE 10 mcg for 7 days). Patient satisfaction was the primary endpoint.
There was no statistically significant difference in the rate of satisfied patients at 12-month follow up between the two study groups, 82.2% and 68.4% in Group A and Group B respectively (p = 0.143). At 6 and 12-months, there was a significant amelioration in the intensity of all pain in both groups. The median number of days of unscheduled bleeding during the first cycle was significantly higher in Group B compared to Group A.
Both NETA and extended-cycle OC are effective in treating pain symptoms related to endometriosis. Extended-cycle OC may cause more unscheduled bleeding, but the rate of satisfaction for those who completed the treatment was similar in the two groups.
Copyright © 2018 Elsevier B.V. All rights reserved.
Biol Reprod. 2018 Feb 2. doi: 10.1093/biolre/ioy030. [Epub ahead of print]
Effects of histone methyltransferase inhibition in endometriosis.
Although the histone methyltransferase EZH2 and its product H3K27me3 are well studied in cancer, little is known about their role and potential as therapeutic targets in endometriosis. We have previously reported that endometriotic lesions are characterized by global enrichment of H3K27me3. Therefore, we aimed to 1) characterize the expression levels of EZH2 in endometriotic tissues, 2) assess H3K27me3 enrichment in candidate genes promoter regions, and 3) determine if pharmacological inhibition of EZH2 impacts migration, proliferation, and invasion of endometriotic cells. Immunohistochemistry (IHC) of an endometriosis-focused tissue microarray (TMA) was used to assess the EZH2 protein levels in tissues. Chromatin Immunoprecipitation (ChIP)-qPCR was conducted to assess enrichment of H3K27me3 in candidate gene promoter regions in tissues. Immunofluorescence (IF) was performed to assess the effect of an EZH2-specific pharmacologic inhibitor on H3K27me3 global enrichment in cells lines. To measure effects of the inhibitor in migration, proliferation, and invasion in vitro we used Scratch, BrdU, and Matrigel assays, respectively. Endometriotic lesions had significantly higher EZH2α nuclear immunostaining levels compared to eutopic endometrium from patients (glands, stroma) and controls (glands). H3K27me3 was enriched within promoter regions of candidate genes in some but not all of the endometriotic lesions. Inhibition of EZH2 reduced H3K27me3 levels in the endometriotic cells specifically, and also reduced migration, proliferation but not invasion of endometriotic epithelial cells (12Z). These findings support future pre-clinical studies to determine in vivo efficacy of EZH2 inhibitors as promising non-hormonal treatments for endometriosis, still an incurable gynecological disease.
Am J Obstet Gynecol. 2018 Feb 2. pii: S0002-9378(18)30084-X. doi: 10.1016/j.ajog.2018.01.035. [Epub ahead of print]
Cine MRI during spontaneous cramps in women with menstrual pain.
The lack of noninvasive methods to study dysmenorrhea has resulted in poor understanding of the mechanisms underlying pain, insufficient diagnostic tests, and limited treatment options. To address this knowledge gap, we have developed a magnetic resonance imaging-based strategy for continuously monitoring the uterus in relationship to participants’ spontaneous pain perception.
The study objective was to evaluate whether magnetic resonance imaging can detect real-time changes in myometrial activity during cramping episodes in women with dysmenorrhea, with a handheld squeeze bulb for pain reporting.
Sixteen women with dysmenorrhea and 10 healthy control women both on and off their menses were evaluated with magnetic resonance imaging while not taking analgesic medication. Continuous magnetic resonance imaging was acquired using half-Fourier acquisition single-shot turbo spin echo sequence along with simultaneous reporting of pain severity with a squeeze bulb. Pearson’s coefficient was used to compare results between reviewers. Proportional differences between women with dysmenorrhea and controls on/off menses were evaluated with a Fisher exact test. The temporal relationships between signal changes were evaluated with Monte Carlo simulations.
Spontaneous progressive decreases in myometrial signal intensity were more frequently observed in women on their menses than in the absence of pain in the same women off their menses or participants without dysmenorrhea (P < .01). Women without reductions in myometrial signal intensity on their menses either had a history of endometriosis or were not in pain. Observations of myometrial events were consistently reported between 2 raters blinded to menstrual pain or day status (r = 0.97, P < .001). Episodes of cramping occurred either immediately before or 32-70 seconds after myometrial signal change onset (P < .05).
Transient decreases in myometrial uterine T2-weighted signal intensity can be reliably measured in women with menstrual pain. The directionality of signal change and temporal relationship to pain onset suggest that cramping pain may be caused by a combination of uterine pressure and hemodynamic dysfunction.
Front Physiol. 2018 Jan 23;9:14. doi: 10.3389/fphys.2018.00014. eCollection 2018.
Discovery of Phosphatidic Acid, Phosphatidylcholine, and Phosphatidylserine as Biomarkers for Early Diagnosis of Endometriosis.
The sensitivity and specificity of clinical diagnostic indicators and non-invasive diagnostic methods for endometriosis at early stage is not optimal. Previous studies demonstrated that abnormal lipid metabolism was involved in the pathological development of endometriosis. Our cross-sectional study included 21 patients with laparoscopically confirmed endometriosis at stage I-II and 20 infertile women who underwent diagnostic laparoscopy combined with hysteroscopy from January 2014 to January 2015. Eutopic endometrium was collected by pipelle endometrial biopsy. Lipid metabolites were quantified by ultra-high performance liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (UHPLC-ESI-HRMS). Lipid profiles of endometriosis patients at early stage (I-II) was characterized by a decreased concentration of phosphatidylcholine (18:1/22:6), (20:1/14:1), (20:3/20:4), and phosphatidylserine (20:3/23:1) and an increased concentration of phosphatidic acid (25:5/22:6) compared with control. The synthesized predicting strategy with 5 biomarkers has a specificity of 75.0% and a sensitivity of 90.5%. Lipid profile of eutopic endometrium in endometriosis was effectively characterized by UHPLC-ESI-HRMS-based metabolomics. Our study demonstrated the alteration of phosphatidic acid, phosphatidylcholine, phosphatidylserine metabolites in endometriosis and provided potential biomarkers for semi-invasive diagnose of endometriosis at early stage.
Case Rep Obstet Gynecol. 2017;2017:2302568. doi: 10.1155/2017/2302568. Epub 2017 Dec 19.
Retroperitoneal Endometriotic Cyst Infiltrated in the Iliopsoas Incidentally Found in a Patient with Acute Back Pain.
We describe a rare case of retroperitoneal endometriotic cyst infiltrated in the iliopsoas incidentally found in a patient with acute back pain. Endometriosis at the pelvic peritoneum, including the Douglas pouch, has been reported often; there are few reports of cystic endometriosis in the retroperitoneal cavity. Today there are various theories regarding how endometriosis occurs. By pathological findings and lesion sites of the present case, we concluded that the endometrial tissues in the menstrual blood might metastasize lymphatically and implant and form the retroperitoneal cyst.
J Pharm Biomed Anal. 2018 Apr 15;152:165-172. doi: 10.1016/j.jpba.2018.01.034. Epub 2018 Jan 31.
Analysis by LC-MS/MS of endogenous steroids from human serum, plasma, endometrium and endometriotic tissue.
An LC-MS/MS method was developed and validated to analyze simultaneously estrogens (estradiol, E2; estrone, E1), androgens (testosterone, T; androstenedione, A4; dehydroepiandrosterone, DHEA), progestagens (17a-hydroxypregnenolone, 17OHP5; 17a-hydroxyprogesterone, 17OHP4; progesterone, P4), glucocorticoids (cortisol, F; cortisone E; corticosterone, B; 11-deoxycortisol, S; 21-hydroxyprogesterone, 21OHP4), and mineralocorticoids (aldosterone, A) from 150 μl of human serum, plasma, or endometrium and endometriotic tissue homogenates. Samples spiked with isotope-labeled steroids as internal standards were extracted with toluene prior to LC-MS/MS analysis. The chromatographic separation of underivatized steroids was achieved on a biphenyl column with 0.2 mM NH4F as the eluent additive and a water-methanol gradient to improve E2 and E1 ionization. Method validation was performed with human plasma samples, and analysis of certified E2, T, F, and P4 reference serums (BCR-576, ERM-DA346, ERM-DA192, ERM-DA347), as well as homogenates of endometrium and endometriotic tissue. A total of 27 steroids were included in the method development to ensure the specificity of the method. After validation, the method was found suitable for quantitative analysis of 11 steroids: E2 (6.7 pM-13 nM), E1 (1.3 pM-6.6 nM), T (3.3 pM-13 nM), A4 (13 pM-33 nM), 17OHP5 (32 pM-65 nM), 17OHP4 (33 pM-13 nM), F (33 pM-133 nM), E (13 pM-130 nM), B (33 pM-134 nM), S (13 pM-129 nM), and A (32 pM-32 nM). In addition, DHEA (333 pM-32 nM), P4 (13 pM-13 nM) and 21OHP4 (13 pM-13 nM) can be analyzed semiquantitatively.
Psychoneuroendocrinology. 2018 Jan 5;89:216-222. doi: 10.1016/j.psyneuen.2018.01.001. [Epub ahead of print]
Hair cortisol and the relationship with chronic pain and quality of life in endometriosispatients.
Endometriosis is a chronic estrogen-dependent disease in which pelvic pain is the dominant symptom. The negative effects of endometriosis on the life of women with this disease can be a cause of stress. Stress levels can be measured in different ways, mostly reflecting acute stress responses. Hair cortisol measurements are a reflection of long-term systematic cortisol levels. In this study a first attempt is made to measure cortisol levels in hair of endometriosis patients in comparison with healthy controls. Moreover, it is explored whether chronic pain symptoms as well as different aspects of Health Related Quality of Life (HRQoL) are associated with hair cortisol levels in women with endometriosis. Results show that the mean hair cortisol level is significantly higher in women with endometriosis compared to healthy controls (p = 0.018). There is a positive correlation between hair cortisol level and HRQoL in patients but not in controls (Rho 0.426). The level of hair cortisol does not correlate with the reported pain intensity in patients (Rho -0.082). These results are indicative of an altered HPA-axis function in endometriosis patients, possibly caused by higher chronic stress level in these patients. Moreover, a potential explanation for the positive correlation of cortisol with the HRQoL in these patients is that patients with a high HRQoL have an adequate stress response by increasing their cortisol levels as a response to physical and emotional stress induced by the endometriosis.
Arch Gynecol Obstet. 2018 Apr;297(4):977-984. doi: 10.1007/s00404-018-4691-y. Epub 2018 Feb 7.
Depleted lamin B1: a possible marker of the involvement of senescence in endometriosis?
Endometriosis is a benign disease characterized by implantation and the growth of endometrial tissue outside the uterine cavity and it shares similarities with cancer. Lamin B1, p16 and p21 play a role on cell cycle regulation, development, cell repair and its activities are related to cancers. Considering the similarities between endometriosis and cancer, the aim of the present cross-sectional study is to detect p16, p21 and Lamin B1 in the ectopic endometrium of patients with endometriosis(n = 8) with eutopic (n = 8) and control endometrium (n = 8) and relate them to the maintenance and development of endometriosis.
Biopsies were obtained from both eutopic and ectopic, from deep infiltrating lesions, endometrium frozen and used for immunofluorescent (p16) or immunohistochemistry procedures (p16, p21, lamin B1).
Detected higher lamin B1 in the eutopic endometrium when compared with ectopic endometrium, with no differences between endometriosis tissue with control endometrium. Similar presence of p16 in all groups of patients and no p21 detection was observed.
We observed reduced detection of lamin B1 in the ectopic endometrium raising the possibility that the presence of senescent cells might be contributing to the maintenance and progression of endometriosis by apoptosis resistance and peritoneal stress inherent of the disease.
Arch Gynecol Obstet. 2018 Apr;297(4):985-988. doi: 10.1007/s00404-018-4692-x. Epub 2018 Feb 7.
Surgical laparoscopic treatment of bowel endometriosis with transvaginal resection of the rectum using ultrasonically activated shears: a retrospective cohort study with description of technique.
To asses the results of laparoscopic surgical treatment of bowel endometriosis with transvaginal resection of the rectum employing ultrasonic energy retrospective study.
100 patients with symptoms of narrowing or partial obstruction of colon were submitted to laparoscopic resection of rectosigmoid tract through a vaginal route. Length of surgery, blood loss, histopathological extent of rectal invasion, surgical complications, and length of hospital stay were the main analyzed outcomes.
Mean operative time was 281 min, blood loss was 250 ml on average, length of stay was 8 days, bowel movements were after 3.5 days, the mean length of bowel-resected segments was 13.3 cm, the disease was multifocal in 64% and multicentric in 36% of surgical specimens.
Laparoscopically assisted vaginal resection of rectosigmoid colon affected by endometriosis using ultrasonically activated shears with mechanical intestinal anastomoses tension free is a safe and effective procedure for surgical management of severe pelvic endometriosis with bowel involvement.
Ultrasound Obstet Gynecol. 2018 Feb 8.
Imaging in gynecological disease: clinical and ultrasound characteristics of endometrioid ovarian cancer.
Moro F1, Magoga G1, Pasciuto T1, Mascilini F2, Moruzzi MC2,3, Fischerova D3, Savelli L4, Giunchi S4, Mancari R5, Franchi D5, Czekierdowski A6, Froyman W7, Verri D8, Epstein E9, Chiappa V10, Guerriero S11, Zannoni GF12, Timmerman D7, Scambia G1, Valentin L13, Testa AC1.
To describe the clinical and ultrasound characteristics of ovarian pure endometrioid carcinoma.
This is a retrospective multicenter study. From the International Ovarian Tumor Analysis (IOTA) database we identified 161 patients with a histological diagnosis of pure endometrioid carcinoma, who had undergone preoperative ultrasound examination by an experienced ultrasound examiner between 1999 and 2016. Another 78 patients with a histological diagnosis of pure endometrioid carcinoma were identified from the databases of the departments of gynecological oncology in the participating centers. All tumors were described using IOTA terminology. In addition, one author reviewed all available ultrasound images and described them using pattern recognition.
Median age of the 239 patients was 55 (range, 19-88) years. On ultrasound examination, two (0.8%) endometrioid carcinomas were described as unilocular cysts, three (1.3%) as multilocular cysts, 37 (15.5%) as unilocular-solid cysts, 115 (48.1%) as multilocular-solid cysts and 82 (34.3%) as solid masses. The largest tumor diameter was median 102.5 (range 20-300) mm and the largest diameter of the largest solid component was median 63 (range 9-300) mm. Papillary projections were present in 70 (29.3%) masses. Most cancers (188, 78.7%) were unilateral. In 49 (20.5%) cases, the cancer was judged by the pathologist to arise in endometriosis. These cancers more often manifested papillary projections on ultrasound than those without evidence of tumor arising in endometriosis (46.9% vs 24.7%; 23/49 vs 47/190), were less often bilateral (8.2% vs 24.7%; 4/49 vs 47/190) and less often associated with ascites (6.1% vs 28.4%; 3/49 vs 54/190) and fluid in the pouch of Douglas (24.5% vs 48.9%; 12/49 vs 93/190). Retrospective analysis of available ultrasound images using pattern recognition revealed that many tumors without evidence of tumor arising in endometriosis (36.3%; 41/113) had a large central solid component entrapped within locules giving the tumor a cockade-like appearance.
Endometrioid cancers are usually large, unilateral, multilocular-solid or solid tumors. The ultrasound characteristics of endometrioid carcinomas arising in endometriosis differ from those without evidence of tumor arising in endometriosis, cancers arising in endometriomas more often being unilateral cysts with papillary projections and no ascites.