Association of endometrioid ovarian carcinoma arising from endometriosis, endometrioid endometrial carcinoma, and high-grade undifferentiated endometrial sarcoma. a case report

Endometriosis is a chronic disease that affects women of reproductive age. Malignant transformation in endometriosis is considered to be an unusual event, only occurring in 0.7-0.1% of cases. However the association between endometriosis and endometrial cancer is not well defined. Also in literature, rare cases of uterine sarcoma, about 3% of all uterine malignancies, associated with endometriosis have been reported. The authors report a case of a 47-years-old Italian woman with histologic diagnosis of endometrioid ovarian carcinoma arising from endometriosis, endometrioid endometrial carcinoma, and undifferentiated endometrial sarcoma. Therefore there have been few studies addressing the relationship between endometrial stromal sarcomas (ESS), and endometriosis. Novel scientific findings are necessary to investigate a possible common pathway and an effective treatment, although complete tumor resection can reduce the recurrence rate

Protein Expression of Steroid Receptors in Macaca mulatta endometriotic Lesions

Endometriosis is pathologically defined as the presence of endometrial tissue in ectopic locations. Currently, there are no specific, non-invasive biomarkers and no cure for endometriosis. Non-human primates (NHP), including Macaca mulatta (rhesus macaques), have been highlighted as appropriate models to study endometriosis due to genetic, physiological, and anatomical similarities to humans. Research shows endometriosis might be associated with molecular deviations in human peritoneal endometriosis, such as increased levels of estrogen receptors and decreased levels of progesterone receptors. The aim of this study is to determine protein expression of steroid receptors in five endometriotic lesions of rhesus macaques. We propose that lesions of rhesus macaques will express elevated estrogen receptors and diminished progesterone receptors, similar to human endometriotic lesions. Endometriotic lesions of rhesus macaques were obtained at time of surgery from different locations, and steroid receptor expression was determined by immunohistochemistry. This study was able to determine the expression of steroid receptors in endometriotic lesions of rhesus macaques; however the results were not able to support our hypothesis. Results did not observe significant differences between estrogen and progesterone receptor protein expressions in glandular and stromal compartments of the endometriotic lesions. Still, this animal model represents a valuable tool to study endometriosis since they do develop spontaneous endometriosis. Future studies should match the location of lesions and classify the severity of endometriosis in the rhesus macaques

A polymorphism in a let-7 microRNA binding site of KRAS in women with endometriosis.

Endometriosis is found in 5-15% of women of reproductive age and is more frequent in relatives of women with the disease. Activation of KRAS results in de novo endometriosis in mice, however, activating KRAS mutations have not been identified in women. We screened 150 women with endometriosis for a polymorphism in a let-7 microRNA (miRNA) binding site in the 3'-UTR of KRAS and detected a KRAS variant allele in 31% of women with endometriosis as opposed to 5% of a large diverse control population. KRAS mRNA and protein expression were increased in cultured endometrial stromal cells of women with the KRAS variant. Increased KRAS protein was due to altered miRNA binding as demonstrated in reporter assays. Endometrial stromal cells from women with the KRAS variant showed increased proliferation and invasion. In a murine model, endometrial xenografts containing the KRAS variant demonstrated increased proliferation and decreased progesterone receptor levels. These findings suggest that an inherited polymorphism of a let-7 miRNA binding site in KRAS leads to abnormal endometrial growth and endometriosis. The LCS6 polymorphism is the first described genetic marker of endometriosis risk

Serum dioxin concentrations and endometriosis: a cohort study in Seveso, Italy.

Dioxin, a ubiquitous contaminant of industrial combustion processes including medical waste incineration, has been implicated in the etiology of endometriosis in animals. We sought to determine whether dioxin exposure is associated with endometriosis in humans. We conducted a population-based historical cohort study 20 years after the 1976 factory explosion in Seveso, Italy, which resulted in the highest known population exposure to 2,3,7,8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD). Participants were 601 female residents of the Seveso area who were (3/4) 30 years old in 1976 and had adequate stored sera. Endometriosis disease status was defined by pelvic surgery, current transvaginal ultrasound, pelvic examination, and interview (for history of infertility and pelvic pain). "Cases" were women who had surgically confirmed disease or an ultrasound consistent with endometriosis. "Nondiseased" women had surgery with no evidence of endometriosis or no signs or symptoms. Other women had uncertain status. To assess TCDD exposure, individual levels of TCDD were measured in stored sera collected soon after the accident. We identified 19 women with endometriosis and 277 nondiseased women. The relative risk ratios (RRRs) for women with serum TCDD levels of 20.1-100 ppt and >100 ppt were 1.2 [90% confidence interval (CI) = 0.3-4.5] and 2.1 (90% CI = 0.5-8.0), respectively, relative to women with TCDD levels (3/4) 20 ppt. Tests for trend using the above exposure categories and continuous log TCDD were nonsignificant. In conclusion, we report a doubled, nonsignificant risk for endometriosis among women with serum TCDD levels of 100 ppt or higher, but no clear dose response. Unavoidable disease misclassification in a population-based study may have led to an underestimate of the true risk of endometriosis

Cutaneous endometriosis.

Cutaneous endometriosis is a disorder that primarily affects women of reproductive age. The disorder is most commonly associated with cyclical pain during menses, but it can be difficult to diagnose in the absence of these symptoms and requires biopsy testing for a definitive diagnosis. We report on a case of a 41-year-old patient undergoing hormonal therapy for infertility who presented with a painful firm subcutaneous nodule in the umbilicus. She was ultimately diagnosed with cutaneous endometriosis and underwent surgical excision. In this report, we discuss the differential diagnosis and comment on treatment options, including surgical excision with wide margins or treatment with hormonal agents, such as danazol or leuprolide. Finally, we discuss whether patients with cutaneous endometriosis should receive an additional evaluation for pelvic endometriosis

Shedding Light on Endometriosis: Patient and Provider Perspectives on a Challenging Disease

Background: Endometriosis is a serious yet understudied medical condition impacting millions of women worldwide. Methods: This mixed methods study aimed to understand health care provider perceptions and patient experiences with endometriosis in the United States. Providers were surveyed to assess their understanding of disease prevalence. A subset of providers also participated in short, open-ended interviews about treating patients who have or are suspected to have endometriosis. Interviews were also conducted with women diagnosed with endometriosis to understand their experiences with the disease. Means and frequencies were calculated for survey data; interviews were transcribed and separately analyzed by two coders using an iterative coding process until agreement was reached. Results: Fifty-three providers completed surveys. Six out of 53 providers (11%) accurately identified the prevalence of endometriosis. Four providers and 12 patients completed interviews. Emergent themes among providers included limited training, difficulty of diagnosis, complexity of the referral process, a challenging patient-provider dynamic, and the importance of multidisciplinary collaboration. Emergent themes from patients included the psychological impact of the disease, difficulties interacting with the healthcare system, self-advocacy, quality of life, and limited treatment options. Conclusion: Providers are frequently unfamiliar with the far-reaching scope of endometriosis and cite many challenges caring for patients with the disease. Patients equally find the disease challenging to live with as it encroaches on physical, mental, and emotional well-being

Long-Term Effects of Traditional Chinese Medicine and Hypnotherapy in Patients with Severe Endometriosis - a Retrospective Evaluation

Background: 15% of patients with severe endometriosis suffer from pain symptoms in spite of pharmacological and surgical treatments. In this retrospective study we aimed to assess the effectiveness of a combined therapy of Traditional Chinese medicine and hypnotherapy (systemic autoregulation therapy, SART) as a novel treatment for endometriosis-associated symptoms. Patients and Methods: 47 patients with severe endometriosis, which were treated with SART, were followed-up by standardized telephone interviews. Follow-up data were compared to baseline assessments. Results: Median follow-up time was 5 years. The median intensity of endometriosis-associated pain had decreased from 8 to 3 points on a 0-10 point visual analogue scale (p < 0.001). 18 patients (38%) were free of pain, and the number of patients using pain medication had decreased from 38 to 19 (from 81% to 40%). 17 out of the 31 women trying for a pregnancy (55%) showed a total of 21 births at follow-up. Exploratory analyses revealed that larger decreases in pain scores correlated significantly with longer treatment durations, suggesting a dose-response relationship. Conclusion: Treatment of endometriosis with a holistic approach of Chinese medicine and hypnotherapy may result in a substantial reduction of pain as well as increased birth rates in patients with therapy-refractory endometriosis. Randomized controlled studies to further investigate the effectiveness of SART are highly warranted

Endometriosis: 10 keys points for MRI

Endometriosis is a chronic disease and a clinical problem in women of fertile age, with a high impact on quality of life, work productivity and health care management. Two imaging modalities are employed in the diagnosis and evaluation of extent of disease: ultrasound examination with endovaginal approach and magnetic resonance imaging (MRI). MRI, thanks to its high contrast and resolution characteristics, offers a high level of accuracy in the study of endometriosis and adenomyosis. We illustrate here 10 key MRI points for the detection and diagnosis of endometriosis