'Guess who'? An Italian multicentric study on pigmentation traits prevalence in endometriosis localizations.

OBJECTIVES: Previous evidence seems to support the more common presence of certain pigmentation types in women with endometriosis. The aim of this study was to assess the association of certain somatic phenotypes with specific localizations of the disease. The genetic makeup of those somatic traits may will help in better define the disease pathogenesis. STUDY DESIGN: Multicentric, retrospective study of women aged 18 to 45 with histologically confirmed endometriosis. 575 patients were recruited at eleven different Italian endometriosis clinics from March 2015 to January 2021. Data regarding clinical and surgical features were recorded following the self-administered endometriosis patient questionnaire and the surgical standard of reports approved by the World Endometriosis Research Foundation (WERF). Pigmentation types/somatic phenotypes frequencies among endometriosis localizations were reported. A logistic regression analysis was performed to determine somatic types independently associated with disease' localizations. RESULTS: Having green eyes increased by ∼4 folds (OR 3.7; 95% CI: 1.42-9.61; p = 0.007) the risk of having a ureteral nodule, whereas brown/black eyes decreased this risk (OR 0.34; 95% CI: 0.13-0.87; p = 0.025). Consistently, the combination of green eyes and blonde/light brown hairs increased the odds of ureteral endometriosis by more than 5 folds (OR 5.40; 95%CI: 2.02-14.49; p = 0.001), even after correction for anthropometric confounders (aOR 5.85; 95% CI: 2.13-16.09; p < 0.001). CONCLUSIONS: The association between endometriosis and pigmentary traits has been herein confirmed, with the novel finding of the possible predisposition of ureteral endometriosis in patients with green eyes and blonde/light brown hairs. Further investigation on the genetic makeup of somatic traits may provide new inroads also into the molecular aspects of endometriosis leading to a better understanding of this complex disease.

Impact of endometriosis on obstetric outcome after natural conception: a multicenter Italian study.

PURPOSE: To evaluate obstetric outcome in women with endometriosis who conceive naturally and receive standard obstetric care in Italy. METHODS: Cases were consecutive women with endometriosis managed in eleven Italian referral centers. Controls were women in whom endometriosis was excluded. All women filled in a questionnaire addressing previous natural pregnancies. Marginal logistic regression models were fitted to evaluate the impact of endometriosis on obstetric outcome. A post hoc analysis was performed within the endometriosis group comparing women with severe adenomyosis versus women with absent or mild adenomyosis. RESULTS: Three hundred and fifty-five pregnancies in endometriosis group and 741 pregnancies in control group were included. Women with endometriosis had a higher risk of preterm delivery < 34 weeks (6.4% vs 2.8%, OR 2.42, 95% CI 1.22-4.82), preterm delivery < 37 weeks (17.8% vs 9.7%, OR 1.98, 95% CI 1.23-3.19), and neonatal admission to Intensive Care Unit (14.1% vs 7.0%, OR 2.04, 95% CI 1.23-3.36). At post hoc analysis, women with endometriosis and severe adenomyosis had an increased risk of placenta previa (23.1% vs 1.8%, OR 16.68, 95% CI 3.49-79.71), cesarean delivery (84.6% vs 38.9%, OR 8.03, 95% CI 1.69-38.25) and preterm delivery < 34 weeks (23.1% vs 5.7%, OR 5.52, 95% CI 1.38-22.09). CONCLUSION: Women with endometriosis who conceive naturally have increased risk of preterm delivery and neonatal admission to intensive care unit. When severe adenomyosis is coexistent with endometriosis, women may be at increased risk of placenta previa and cesarean delivery. TRIAL REGISTRATION: Clinical trial registration number: NCT03354793.

High prevalence of autoimmune diseases in women with endometriosis: a case-control study.

The immune system seems to be involved in the pathogenesis of endometriosis. Peritoneal chronic inflammation is present and natural killer cells and macrophages abnormalities have been reported in women with the disease. Moreover, a higher production of serum autoantibodies has been found, which could be related to various factors; some still need to be clarified. The correlation between endometriosis and autoimmune diseases is still unclear with few and conflicting available data. The aim of this study was to evaluate the prevalence of autoimmune diseases, as conditions with a possible common pathogenetic factor, in women affected by endometriosis, in order to address future research on its pathogenesis. This retrospective case-control study includes one hundred and forty-eight women with endometriosis and 150 controls. All women were aged between 18 and 45. Informed consent was obtained from all participants of the study. Considered autoimmune diseases include systemic lupus erythematosus (SLE), celiac disease (CD), inflammatory bowel disease (IBD), and autoimmune thyroiditis. Statistical comparison of patients and control group was performed by means of chi-square test or Fisher's exact test as appropriate. Statistical comparison of parametric variable (age) among the groups was performed by t-test for unpaired data. Age was expressed as mean. A value of .05 or less was considered as significant. In the case group, five patients were affected by IBD, while the disease was not observed in the control group (p = .07). SLE was found in eight patients in the case group, while only one was found in the control group (p = .01). Fifteen women in the case group were affected by CD, while the disease was present only in one woman in the control group (p<.0001). A significant correlation was also found between endometriosis and autoimmune thyroiditis: 80 patients with endometriosis had thyroid diseases versus 14 patients in the control group (p<.0001). Our study reports an association between endometriosis and autoimmune disorders, showing a higher prevalence of autoimmune diseases in women affected by endometriosis. These results support a possible autoimmune pathogenesis of endometriosis.

Spontaneous hemoperitoneum in a pregnancy with endometriosis.

The protective effect of pregnancy on endometriosis is well known, but complications related to the pregnant state, such as hemoperitoneum, uroperitoneum and bowel perforation may occur.

Endometriosis: seeking optimal management in women approaching menopause.

The incidence of endometriosis in middle-aged women is not minimal compared to that in the reproductive age group. The treatment of affected women after childbearing age to the natural transition toward menopause has received considerably poor attention. Disease management is problematic for these women due to increased contraindications regarding hormonal treatment and the possibility for malignant transformation, considering the increased cancer risk in patients with a long-standing history of the disease. This state-of-the-art review aims for the first time to assess the benefits of the available therapies to help guide treatment decisions for the care of endometriosis in women approaching menopause. Progestins are proven effective in reducing pain and should be preferred in these women. According to the international guidelines that lack precise recommendations, hysterectomy with bilateral salpingo-oophorectomy should be the definitive therapy in women who have completed their reproductive arc, if medical therapy has failed. Strict surveillance or surgery with removal of affected gonads should be considered in cases of long-standing or recurrent endometriomas, especially in the presence of modifications of ultrasonographic cyst patterns. Although rare, malignant transformation of various tissues in endometriosis patients has been described, and management is herein discussed.

Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutated patients: An evidence-based approach on what women should know.

This review is focused on the ovarian cancer risk reduction management in BRCA mutation carriers and is intended to assist with clinical decision-making. Obviously, treatment decisions must be based on the available evidence. Despite risk-reducing salpingo-oophorectomy is firmly recommended, several separate questions can be raised to address the variety of intense controversy of this approach. A special emphasis lies in the effective preventive surgical measure against ovarian cancer risk, in an attempt to detect the optimal timing and mitigate the impact on patients. The long term implications of risk-reducing salpingo-oophorectomy as well as hormone replacement therapy are also actively debated. This is expected to represent an opportunity for improved management modelling of BRCA mutated patients.

Endometriosis and Glanzmann’s thrombasthenia.

Glanzmann’s thrombasthenia (GT) is a rare bleeding syndrome characterized by deficiency or defect of platelet aggregation complex. The pathogenesis of endometriosis is controversial but the strongest evidence leans towards retrograde menstruation. GT probably predisposes to endometriosis. The management of women affected by this disease can be difficult due to the risk of bleeding complications, especially during surgical treatment. We describe the cases of three sisters affected by endometriosis and GT, referred to our Department, who received different therapeutic management.

praja2 regulates KSR1 stability and mitogenic signaling.

The kinase suppressor of Ras 1 (KSR1) has a fundamental role in mitogenic signaling by scaffolding components of the Ras/MAP kinase pathway. In response to Ras activation, KSR1 assembles a tripartite kinase complex that optimally transfers signals generated at the cell membrane to activate ERK. We describe a novel mechanism of ERK attenuation based on ubiquitin-dependent proteolysis of KSR1. Stimulation of membrane receptors by hormones or growth factors induced KSR1 polyubiquitination, which paralleled a decline of ERK1/2 signaling. We identified praja2 as the E3 ligase that ubiquitylates KSR1. We showed that praja2-dependent regulation of KSR1 is involved in the growth of cancer cells and in the maintenance of undifferentiated pluripotent state in mouse embryonic stem cells. The dynamic interplay between the ubiquitin system and the kinase scaffold of the Ras pathway shapes the activation profile of the mitogenic cascade. By controlling KSR1 levels, praja2 directly affects compartmentalized ERK activities, impacting on physiological events required for cell proliferation and maintenance of embryonic stem cell pluripotency.

Diffusion tensor imaging and tractography to evaluate sacral nerve root abnormalities in endometriosis-related pain: a pilot study.

OBJECTIVE: To prospectively evaluate microstructural abnormalities in sacral nerve roots in women affected by chronic pelvic pain associated with endometriosis. METHODS: We enrolled 30 women with an ultrasound diagnosis of endometriosis and moderate-severe chronic pelvic pain; 10 age-matched healthy women comprised the control group. All subjects underwent 3 T magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI); the sacral roots were reconstructed by post-processing the DTI data with dedicated software. Mean fractional anisotropy (FA) values in the S1, S2 and S3 roots were quantified. Analysis of FA values was performed by two radiologists in order to evaluate the interobserver agreement. RESULTS: The sacral nerve roots in healthy subjects were clearly visualised. Most of the patients with endometriosis displayed abnormalities of S1, S2 and S3 bilaterally at tractography, including an irregular and disorganised appearance. FA values in the S1, S2 and S3 roots were significantly lower in patients than in controls (P < 0.0001, <0.05 and <0.02, respectively) for both observers. No significant difference was found between observers. CONCLUSION: DTI with tractography is a non-invasive means of detecting changes in the microarchitecture of the sacral nerve roots. It can qualitatively and quantitatively reveal sacral root abnormalities in patients with endometriosis-associated pain. KEY POINTS: • MRI is increasingly used for endometriosis and chronic pelvic pain (CPP). • Magnetic resonance tractography can demonstrate microarchitectural abnormalities in sacral nerve roots. • Tractography shows altered microstructure of sacral roots affected by endometriosis and CPP. • S1-S3 fractional anisotropy values are lower in endometriosis than in healthy women. • Sacral nerve root alteration may explain the nature of endometriosis-related CPP.

Role of environmental organochlorinated pollutants in the development of endometriosis.

Endometriosis is a gynecological disease, which involves the growth of endometrial tissue outside the uterine cavity, commonly in the pelvic region. The etiology of the disease is unclear, but multiple factors may contribute to its pathogenesis. Environmental organochlorinated pollutants, particularly dioxins and polychlorinated biphenyls (PCBs), are thought to play a role in the development of this disease; however, the results of clinical trials are discordant, and it is not clear how the effect of exposure to these compounds is linked to endometriosis. Their effects on cytokines, immune system, hormones, and growth factors are thought to increase the risk of endometriosis. The purpose of this review is to provide an overview of epidemiological studies, which have evaluated the relationship between endometriosis and exposure to persistent organochlorinated pollutants.

Feasibility of 3.0T pelvic MR imaging in the evaluation of endometriosis.

INTRODUCTION: Endometriosis represents an important clinical problem in women of reproductive age with high impact on quality of life, work productivity and health care management. The aim of this study is to define the role of 3T magnetom system MRI in the evaluation of endometriosis. MATERIALS AND METHODS: Forty-six women, with transvaginal (TV) ultrasound examination positive for endometriosis, with pelvic pain, or infertile underwent an MR 3.0T examination with the following protocol: T2 weighted FRFSE HR sequences, T2 weighted FRFSE HR CUBE 3D sequences, T1 w FSE sequences, LAVA-flex sequences. Pelvic anatomy, macroscopic endometriosis implants, deep endometriosis implants, fallopian tube involvement, adhesions presence, fluid effusion in Douglas pouch, uterus and kidney pathologies or anomalies associated and sacral nervous routes were considered by two radiologists in consensus. Laparoscopy was considered the gold standard. RESULTS: MRI imaging diagnosed deep endometriosis in 22/46 patients, endometriomas not associated to deep implants in 9/46 patients, 15/46 patients resulted negative for endometriosis, 11 of 22 patients with deep endometriosis reported ovarian endometriosis cyst. We obtained high percentages of sensibility (96.97%), specificity (100.00%), VPP (100.00%), VPN (92.86%). CONCLUSION: Pelvic MRI performed with 3T system guarantees high spatial and contrast resolution, providing accurate information about endometriosis implants, with a good pre-surgery mapping of the lesions involving both bowels and bladder surface and recto-uterine ligaments.

Asymptomatic struma ovarii: a case report.

Struma ovarii is a rare ovarian neoplasm. This tumor is generally benign, although malignant transformation has been reported. The preoperative diagnosis is generally difficult. Thyroid hormones may be produced and in a few cases asymptomatic women may develop definitive clinical hypothyroidism after resection of struma ovarii. We report a case of a 39-year-old woman who underwent laparoscopic resection of an asymptomatic right ovarian mass. The pathologic diagnosis was struma ovarii. The postoperative period was uneventful and her thyroid function remained normal.

Reproductive outcome after laparoscopic treatment of endometriosis.

PURPOSE OF INVESTIGATION: To evaluate the pregnancy rate after laparoscopic treatment of endometriosis. PATIENTS AND METHODS: 47 infertile women undergoing laparoscopic treatment of endometriosis. RESULTS: rAFS stage was as follows: 11% of patients had Stage I, 11% Stage II, 53.3% Stage III and 24.4% Stage IV. The mean duration of follow-up was 48.5 +/- 18.44 months. The overall pregnancy rate was 64.4%. Eighteen out of 26 women (69%) became pregnant within six months after laparoscopy, 23% at 12 months, 11% within 24 months, and 11% after two years (p < 0.01). Adnexal adhesions and tubal status significantly affected the pregnancy rate. No differences were found regarding the stage of disease and the presence of ovarian endometriomas. CONCLUSION: Laparoscopic treatment of endometriosis enhances fertility and the pregnancy rate is highest within the first six months after surgery. Adnexal adhesions and tubal conditions influence the reproductive outcome.

Serum evaluation of P53 protein in patients with gynaecological cancer.

Sera from patients with gynaecological cancer including the ovary, endometrium or cervix were examined for p53 protein, using the Pantropic p53 quantitative ELISA. Patients with benign gynaecological pathologies were included as a control group. p53 values ranged from undetectable to high levels of the protein (range: 0-531 pg/ml). Using the value of 200 pg/ml as the cut-off, p53 serum levels were found to be elevated in 23% of the patients with ovarian cancer, in 16% of the patients with endometrial cancer and in 14% of the patients with cervical cancer. In the control group, increased serum p53 levels were found in 3.3% of patients. No differences were observed among the groups with different types of cancer or at different stages, but the differences between the cancer groups and the control group were statistically significant. Our results suggest that serum p53 evaluation could be an adjunctive tool to the diagnostic laboratory tests for preoperatively gynaecological cancers and both a competitive and alternative useful procedure for the detection of p53 gene mutations.

Correlation between endometriosis and pelvic pain.

STUDY OBJECTIVE: To evaluate the relationship between prevalence and severity of chronic pelvic pain (CPP) and stage, site, and type of endometriosis. DESIGN: Prospective, observational study (Canadian Task Force classification II-2). SETTING: University Hospital. PATIENTS: Of 90 consecutive women with biopsy-proved endometriosis, laparoscopy was performed in 69 for pelvic pain and in 21 for infertility or clinical and ultrasonographic suspicion of ovarian endometriosis. INTERVENTION: Preoperatively, using a 10-point visual analog scale, the severity of dysmenorrhea, CPP, and deep dyspareunia was assessed. During laparoscopy all visible endometriotic lesions were recorded and treated. MEASUREMENTS AND MAIN RESULTS: Ten women (11.1%) had no pain; 72 had dysmenorrhea (mild in 13, moderate in 37, severe in 22); 55 had CPP (mild in 11, moderate in 25, severe in 19); and 39 deep dyspareunia (mild in 5, moderate in 31, severe in 3). The severity of dysmenorrhea significantly correlated with the presence and extent of pelvic adhesions (p = 0.004); the severity of CPP correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001) and extent of pelvic adhesions (p = 0.02); and deep dyspareunia correlated with deep endometriosis on the uterosacral ligaments (p = 0.04). Total pain score significantly correlated with deep endometriosis on the uterosacral ligaments (p = 0.0001), peritoneal adhesions (p = 0.01), and extent of adnexal adhesions (p = 0.01). No significant correlation was found among revised American Fertility Society stage of endometriosis; presence and size of ovarian endometriomas; extent, type, and site of peritoneal lesions; and pain scores. By logistic regression analysis, the presence and intensity of total pain could be predicted simultaneously by the presence of deep endometriosis (p = 0.0001) and presence and extent of adnexal adhesions without cystic endometriosis (p = 0.01), and by the presence of ovarian endometrioma with periovarian adhesions (p = 0.03). Chronic pelvic pain was predicted by both deep endometriosis (p = 0.0001) and ovarian endometriomas with adnexal adhesions (p = 0.03). Deep dyspareunia was predicted simultaneously by deep endometriosis (p = 0.01) and an ovarian endometrioma with periovarian adhesions (p = 0. 008). Conclusion. Deep endometriosis, pelvic adhesions, and ovarian cystic endometriosis were independent predictors of pelvic pain. These data strongly suggest that it is not the size of ovarian cystic endometriosis but the association with adhesions that causes pelvic pain.

The biophysical/biochemical test. A new marker of fetal lung maturity in borderline cases.

OBJECTIVE: To assess the diagnostic accuracy of the combination of a biophysical (lamellar body count [LB]) with a biochemical test lecithin/sphingomyelin ratio (L/S) for the evaluation of fetal lung maturity (FLM) in cases of intermediate-borderline pulmonary maturity. STUDY DESIGN: We studied 105 cases with one or both intermediate (2.1-2.4:1 for L/S and/or 15,000-19,000/microL for LB) or borderline (2.5:1 for L/S and/or 20,000/microL for LB count) FLM indices and no phosphatidylglycerol who delivered within 72 hours of amniocentesis, excluding multiple gestation and contaminated amniotic fluid samples. The biophysical x biochemical marker (B x B) was calculated by multiplying L/S by the corresponding LB, then dividing by 10(3). By using the ROC curve, a cutoff of 50 was found. RESULTS: B x B values were lower in respiratory distress syndrome (RDS) than in the non-RDS group (30 [23-41] vs. 52 [50-70], P < .001; median, 25-75%). All RDS cases had a B x B value < 50. Diagnostic accuracy for B x B was: sensitivity, 100%; specificity, 83%; positive predictive value, 61%; negative predictive value, 100%. Sensitivity and positive predictive values were higher for B x B than L/S. CONCLUSION: B x B may be a useful tool for cases with borderline FLM.