'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.

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.

Assessment of ovarian reserve after cystectomy versus 'one-step' laser vaporization in the treatment of ovarian endometrioma: a small randomized clinical trial.

STUDY QUESTION: Does CO2 laser vaporization offer better results in treating endometrioma in terms of ovarian reserve preservation compared to traditional cystectomy? SUMMARY ANSWER: Assessing both antral follicle count (AFC) and serum anti-Müllerian hormone (AMH) levels as measures of ovarian reserve, the results suggest that CO2 technology may be an alternative treatment for endometrioma, causing minimal damage to adjacent healthy ovarian tissue. WHAT IS KNOWN ALREADY: Excisional surgery has been questioned as an ideal surgical approach for endometriomas because it is associated with potential reduction of ovarian reserve. Recently, vaporization with CO2 laser in-line-of-sight, according to the 'three-step procedure', has been proposed as the best method to preserve ovarian function. However, no randomized controlled trials have been conducted to compare cystectomy and 'one-step' CO2 fiber laser vaporization (without GnRH agonist therapy) with respect to the ovarian reserve. STUDY DESIGN, SIZE, DURATION: A multicentre randomized clinical trial including 60 patients was performed between July 2017 and February 2018. Computerized randomization was conducted to allocate them in a proportion of 1:1 either to Group 1 (laparoscopic stripping: cystectomy) or Group 2 (CO2 laser vaporization). Patients in Group 1 underwent a standardized laparoscopic stripping technique; patients in Group 2 underwent drainage of the cyst content, biopsy and vaporization of the internal wall with a CO2 fiber laser. Patients underwent pelvic ultrasound examination to determine the AFC and blood sampling to determine AMH levels before surgery and at 1- and 3-month follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients undergoing surgery for symptomatic endometriomas (infertility and/or pelvic pain) larger than 3 cm were randomized in two groups according to the surgical technique. Patients aged ≥40 years, or with deep infiltrating endometriosis/adenomyosis, or previously submitted to surgical procedures on the ovaries or to hysterectomy were excluded from the study. The primary endpoint was the comparison of intra-group AFC changes before and after surgery (ΔAFC) between the two groups (ΔAFC Group 1 versus ΔAFC Group 2). The secondary endpoint was the modification of serum AMH before and after surgery (ΔAMH) between the two groups (ΔAMH Group 1 versus ΔAMH Group 2). MAIN RESULTS AND THE ROLE OF CHANCE: The AFC of the operated ovary was significantly increased in Group 2 (laser vaporization) compared with Group 1 (cystectomy) after surgery (Group 1: from 4.1 ± 2.2 [mean ± SD] at baseline to 6.3 ± 3.5 at 3-month follow-up; 95% CI: 0.9-4; Group 2: from 3.6 ± 1.9 at baseline to 8.6 ± 4.2 at 3-month follow-up; 95% CI: 2.8-7.1; P = 0.016); serum AMH levels were significantly reduced at 3 months in Group 1 (from 2.6 ± 1.4 ng/mL at baseline to 1.8 ± 0.8 ng/mL at 3-month follow-up; 95% CI: -1.3 to -0.2; P = 0.012) compared with no reduction in Group 2 (from 2.3 ± 1.1 ng/mL at baseline to 1.9 ± 0.9 ng/mL at 3-month follow-up; 95% CI: -1 to -0.2; P = 0.09). LIMITATIONS, REASON FOR CAUTION: The key limitations of the trial were the low accuracy of AFC in estimating the ovarian reserve in ovaries with endometriomas, the limited study size and the relatively short follow-up, which do not allow us to draw definitive conclusions. WIDER IMPLICATIONS OF THE FINDINGS: The present study suggests that CO2 technology may treat endometrioma with minimal damage to the adjacent healthy ovarian tissue; however, this study should be considered as a preliminary clinical trial, intended to stimulate future larger trials to address this clinically relevant issue. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03227640. TRIAL REGISTRATION DATE: 9 July 2017. DATE OF FIRST PATIENT'S ENROLLMENT: 24 July 2017.

Adjuvant chemotherapy does not improve disease-free survival in FIGO stage IC ovarian granulosa cell tumors: The MITO-9 study.

OBJECTIVE: Evidence-based management of granulosa cell tumors of the ovary (GCT) has been not yet standardized: surgery, including fertility-sparing procedures for young women, has been traditionally the standard treatment; on the other hand, chemotherapy has been used for treatment of advanced and/or recurrent disease. However, very limited experience, has been selectively focused on the role of adjuvant chemotherapy in stage IC patients. The objective of this retrospective study was to assess the efficacy of first line postoperative chemotherapy in patients with stage IC treated at the Italian Centers involved in the MITO (Multicenter Italian Trials in Ovarian cancer) Group. PATIENTS AND METHODS: A retrospective multi-institutional review of patients with GCT of the ovary at FIGO stage IC treated or referred to MITO centers was conducted. Surgical outcome, pathological findings and follow-up data were analysed. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors factors for disease free survival. RESULTS: A total of 40 patients with primary GCT of the ovary at FIGO stage IC were identified. The median follow-up period was 96months (range 7-300). At multivariate analysis, surgical treatment outside MITO centers and incomplete surgical staging were independent poor prognostic indicators for recurrence; adjuvant chemotherapy did not retain significant predictive value for recurrence. CONCLUSIONS: This study raises the question about the value of adjuvant chemotherapy in stage IC GCT: a comprehensive evaluation of a larger series is urgently needed in order to characterize stage IC substages who can be spared treatment toxicity.

An alternative approach for the treatment of vaginal atrophy.

AIM: The aim of this study was to determine the efficacy of a new topic non-hormonal treatment for postmenopausal women complaining of symptoms of vaginal atrophy. METHODS: Patients included in the study were prescribed Sinecol gel (AM PHARMA Srl, Vimercate, Monza and Brianza, Italy) application once a day for 20 consecutive days. Sinecol gel is a topic compound for vaginal atrophy containing hyaluronic acid, that is known to improve vaginal elasticity, lactoperoxidase, Xantham gum and glucose oxidase, which have protective and antibacterial action. We evaluated each patient before and after treatment, both subjectively with the "Visual Analogical Scale" (VAS) and objectively with the "Vaginal Health Index" (VHI). RESULTS: We observed a significant clinical improvement of the subjective and objective assessment of symptoms severity with a p value <0.001 at the end of the treatment compared to baseline. CONCLUSION: Sinecol gel appears to be an effective and valid non-hormonal alternative to the estrogen therapy for vaginal atrophy.

Comparison of optimal cytoreduction rates in emergency versus non-emergency admissions for advanced ovarian cancer: a multi-institutional study.

AIMS: to investigate whether first referral to the Emergency Department (ED) of a General Hospital is an independent risk-factor for suboptimal debulking compared to a similar population electively admitted to cytoreductive surgery, in a cohort of 307 AOC patients. METHODS: this is a multicentre case-control study, analyzing a cohort of 307 AOC patients treated at San Raffaele Hospital of Milan (111 Center A) and Gemelli Hospital of Rome (196 Center B) between January 2006/2008 and December 2010. Women are classified as patients admitted to the Hospital from ED (Cases) and out-patients (Controls). RESULTS: At univariate analysis, Cases significantly differ from Controls in terms of worse ECOG PS, larger ascites, pleuric effusion and peritoneal carcinomatosis. The rate of optimal cytoreduction is statistically lower in the Cases than Controls. At multivariate analysis, significant independent predictors for suboptimal residual disease resulted ED admission, peritoneal carcinosis and mesenteral involvement, supra radical surgery. CONCLUSIONS: Patients admitted from Emergency Department may have a lower likelihood of optimal cytoreduction, due to their poor clinical characteristics and large diffusion of the disease.

Long-term follow-up is crucial after treatment for granulosa cell tumours of the ovary.

OBJECTIVE: The aim of this study is to evaluate the long-term outcome of granulosa cell tumour (GCT) of the ovary in a large series of patients treated in MITO centres (Multicentre Italian Trials in Ovarian Cancer) and to define prognostic parameters for relapse and survival. METHODS: A retrospective multi-institutional review of patients with GCTs of the ovary treated or referred to MITO centres was conducted. Surgical outcome, intraoperative and pathological findings and follow-up data were analysed. Kaplan-Meier and Cox proportional hazards analyses were used to determine the predictors for survival and recurrence. RESULTS: A total of 97 patients with primary GCT of the ovary were identified. The median follow-up period was 88 months (range 6-498). Of these, 33 patients had at least one episode of disease recurrence, with a median time to recurrence of 53 months (range 9-332). Also, 47% of recurrences occurred after 5 years from initial diagnosis. At multivariate analysis, age and stage were independent poor prognostic indicators for survival; surgical treatment outside MITO centres and incomplete surgical staging retained significant predictive value for recurrence in both univariate and multivariate analyses. CONCLUSIONS: This study confirms the generally favourable prognosis of GCTs of the ovary, with 5-year overall survival approaching 97%. Nevertheless, prognosis after 20 years was significantly poorer, with 20-year survival rate of 66.8% and a global mortality of 30-35. These findings support the need for lifelong follow-up even in early-stage GCT.