Ultrasound features of highly vascularized uterine myomas (uterine smooth muscle tumors) and correlation with histopathology.

OBJECTIVE: To correlate the ultrasound appearance of highly vascularized uterine myomas with their histopathological diagnosis. METHODS: This was a prospective observational study of patients with a preoperative ultrasound diagnosis of a highly vascularized uterine myoma (color score of 3 or 4, according to the Morphological Uterus Sonographic Assessment (MUSA) criteria), characterized by circumferential and intralesional vascular pattern, who underwent myomectomy or hysterectomy. For each patient, ultrasound characteristics were recorded at baseline, including the number of lesions, the size, echogenicity and border regularity of the lesion, presence of cystic areas and shadowing within the myoma, and visualization of the endometrium. Ultrasound features were correlated with the definitive histological diagnosis. Ultrasound features were then compared between malignant and benign lesions. RESULTS: We included 70 patients with highly vascularized uterine myomas on power/color Doppler. Their mean age was 46.5 ± 11.4 years and 13 (18.6%) were postmenopausal. At histological examination, 65 (92.9%) uterine myomas were benign lesions, comprising 32 typical leiomyomas, 29 leiomyoma variants and four adenomyomas. The remaining five (7.1%) uterine myomas were malignant masses, comprising two uterine sarcomas, one leiomyosarcoma, one neuroendocrine tumor and one uterine smooth muscle tumor of uncertain malignant potential (STUMP). The mean age of patients with a malignant lesion was significantly higher than the age of those with a benign lesion (64.8 ± 16.0 vs 42.4 ± 5.1; P < 0.001). Four out of five patients with a malignant lesion were over 45 years old. Ultrasound demonstrated cystic areas within the lesion in 10/32 (31.3%) typical leiomyomas, 16/29 (55.2%) leiomyoma variants, all four adenomyomas and in the cases of STUMP and leiomyosarcoma. Lesion borders were regular in 64/65 (98.5%) benign lesions and 2/5 (40%) malignant lesions (P < 0.05). No significant differences were observed between benign and malignant lesions with respect to echogenicity, presence of shadowing and size. The endometrium was visible in 55/65 women with benign lesions and in 2/5 with malignant lesions (P = 0.03). CONCLUSIONS: Our results showed that ultrasound features of uterine myomas, such as circumferential and intralesional vascularity, cystic areas and lesion borders, are important parameters for differential diagnosis, especially when combined with the patient's age. Such features could be useful to differentiate typical myomas from benign variants and malignant lesions in a preoperative setting and to select patients that may benefit from conservative management rather than surgery. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

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.

Consensus on Recording Deep Endometriosis Surgery: the CORDES statement.

STUDY QUESTION: Which essential items should be recorded before, during and after endometriosis surgery and in clinical outcome based surgical trials in patients with deep endometriosis (DE)? SUMMARY ANSWER: A DE surgical sheet (DESS) was developed for standardized reporting of the surgical treatment of DE and an international expert consensus proposal on relevant items that should be recorded in surgical outcome trials in women with DE. WHAT IS KNOWN ALREADY: Surgery is an important treatment for symptomatic DE. So far, data have been reported in such a way that comparison of different surgical techniques is impossible. Therefore, we present an international expert proposal for standardized reporting of surgical treatment and surgical outcome trials in women with DE. STUDY DESIGN, SIZE, DURATION: International expert consensus based on a systematic review of literature. PARTICIPANTS/MATERIALS, SETTING, METHODS: Taking into account recommendations from Consolidated Standards of Reporting Trials (CONSORT), the Innovation Development Exploration Assessment and Long-term Study (IDEAL), the Initiative on Methods, Measurement and Pain Assessment in Clinical trials (IMMPACT) and the World Endometriosis Research Foundation Phenome and Biobanking Harmonisation Project (WERF EPHect), a systematic literature review on surgical treatment of DE was performed and resulted in a proposal for standardized reporting, adapted by contributions from eight members of the multidisciplinary Leuven University Hospitals Endometriosis Care Program, from 18 international experts and from audience feedback during three international meetings. MAIN RESULTS AND THE ROLE OF CHANCE: We have developed the DESS to record in detail the surgical procedures for DE, and an international consensus on pre-, intra- and post-operative data that should be recorded in surgical outcome trials on DE. LIMITATIONS, REASONS FOR CAUTION: The recommendations in this paper represent a consensus among international experts based on a systematic review of the literature. For several items and recommendations, high-quality RCTs were not available. Further research is needed to validate and evaluate the recommendations presented here. WIDER IMPLICATIONS OF THE FINDINGS: This international expert consensus for standardized reporting of surgical treatment in women with DE, based on a systematic literature review and international consensus, can be used as a guideline to record and report surgical management of patients with DE and as a guideline to design, execute, interpret and compare clinical trials in this patient population. STUDY FUNDING/COMPETING INTERESTS: None of the authors received funding for the development of this paper. M.A. reports personal fees and non-financial support from Bayer Pharma outside the submitted work; H.T. reports a grant from Pfizer and personal fees for being on the advisory board of Perrigo, Abbvie, Allergan and SPD. TRIAL REGISTRATION NUMBER: N/A.

Transvaginal sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis: association with symptoms.

OBJECTIVES: To investigate whether there are sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis and to examine their association with symptoms of dysmenorrhea and abnormal uterine bleeding. METHODS: This was a prospective observational study including women referred from a gynecology outpatient center to our university hospital for ultrasound examination. Inclusion criteria were age between 18 and 30 years, regular menstrual cycle and nulligravid status. Exclusion criteria were a past or current history of endometriosis, fibroids, ovarian cysts or lesions, endometrial pathology, current use of hormonal treatments or medications that would affect the menstrual cycle, previous uterine surgery and history of infertility. Women underwent a detailed clinical assessment and a two- (2D) and three-dimensional (3D) transvaginal ultrasound (TVS) examination. 2D-TVS features associated with diffuse adenomyosis were predefined as: (1) heterogeneous myometrium; (2) hypoechoic striation in the myometrium; (3) myometrial anechoic lacunae or cysts; (4) asymmetrical myometrial thickening of the uterine walls with the presence of straight vessels, extending into the hypertrophic myometrium, on power Doppler examination. On 3D-TVS, endomyometrial junctional zone (JZ) was measured as the distance from the basal endometrium to the internal layer of the outer myometrium on coronal section at any level of the uterus, and the smallest (JZmin) and largest (JZmax) JZ thicknesses and their difference (JZdiff) were recorded. 3D-TVS evaluation was considered suggestive for adenomyosis when JZmax ≥ 8 mm and/or JZdiff ≥ 4 mm. The presence of associated symptomatology represented our main outcome: the amount of menstrual loss was assessed by a pictorial blood loss analysis chart (PBAC) and painful symptoms were evaluated using a visual analog scale (VAS). RESULTS: During the observation period, 205 women (median age, 24 (interquartile range, 23-27) years) were enrolled into the study and 156 met the inclusion criteria. According to the 2D-TVS criteria, diffuse adenomyosis was found in 53 (34.0%) women and asymmetrical myometrial thickening of the uterine walls was the most common sonographic feature observed. ANOVA showed a significant relationship between the number of 2D-TVS features of diffuse adenomyosis and VAS score for dysmenorrhea (P = 0.005) as well as PBAC score for menstrual loss (P = 0.03). 3D-TVS showed that women with 2D-TVS features of diffuse adenomyosis had a significantly higher value of JZmax (6.38 ± 2.30 mm, P < 0.001), JZmin (2.07 ± 0.43 mm, P = 0.002) and JZdiff (4.33 ± 1.99 mm, P < 0.001) than did women without these features. Women with sonographic features of diffuse adenomyosis were symptomatic in 83% of cases, reported dysmenorrhea in 79.2% and showed a higher incidence of heavy bleeding than did those without these features (18.9% vs 2.9%; P = 0.001). CONCLUSIONS: Sonographic features suggestive of diffuse adenomyosis may develop earlier in reproductive life than previously thought, and may occur in association with dysmenorrhea and abnormal uterine bleeding in nulligravid women. Their observation in these women should therefore warrant further gynecological investigation.

Reproducibility of #Enzian classification by transvaginal ultrasound and its correlation with symptoms.

Background: The #Enzian classification represents a system to describe endometriotic lesions during surgery. Its use is well established in correlating ultrasound and surgical findings. Objectives: To describe interobserver reproducibility of ultrasound use and symptom correlation with compartments involved using #Enzian classification. Materials and Methods: Two experienced operators performed transvaginal sonography (TVS) in 52 patients affected by pelvic endometriosis. A rate agreement was determined. A further 200 women with endometriotic TVS signs, with no previous surgery and not taking any hormonal therapy, were staged by one of three different operators according to the #Enzian (compartments A, B, C, O, T, FA, FB, FI, FU, FO). Statistical analysis compared all the compartments, as single or associated, with single or combined symptoms (dysmenorrhea, dyspareunia, heavy menstrual bleeding - HMB, bowel symptoms). Main outcome measures: Evaluation of the reproducibility of #Enzian classification in assessing pelvic endometriosis among different operators using TVS, and of possible associations between symptoms and specific #Enzian compartments. Results: Excellent agreement between the two operators in evaluating almost all the compartments (k >0.8) was observed. Dysmenorrhea did not correlate with any specific compartment. We observed a significant association between dyspareunia and B compartment (p=0.02). HMB is associated with FA (p=0.02). Bowel symptoms were associated with B (p=0.02). Combining more symptoms, we observed more significant associations with different compartments. Conclusions: #ENZIAN classification is reproducible in the evaluation of pelvic endometriosis. Some symptoms are correlated to specific ultrasound signs of the disease. What is new?: An accurate evaluation of symptoms could guide TVS examination to detect specific endometriotic lesions and establish the best management for the patients.

The anatomy of the pelvic plexus in female cadavers: implications for retroperitoneal nerve-sparing surgery.

Background: The inferior hypogastric plexus (IHP) is a crucial structure for female continence and sexual function. A nerve-sparing approach should be pursued to reduce the risk of pelvic plexus damage during retroperitoneal pelvic surgery. Objectives: To analyse the relationship between the female IHP and several pelvic anatomical landmarks. Materials and Methods: Standardised cadaveric dissection was performed on 5 nulliparous female cadavers. The relationships of the IHP and the mid-cervical plane (MCP), the mid-sagittal plane (MSP), and the uterosacral ligament (USL) were investigated. Main outcome measures: Distance between IHP and MCP, MSP, and USL. Results: Distances between the right IHP and the right MSP (mean distance: 16.3 mm; range: 10.0-22.5 mm) and the right USL (mean distance: 4.8 mm; range: 0-15.0 mm) were shorter than those between the left IHP and ipsilateral landmarks (left MSP distance: 23.5 mm; range 18.0-30.0 mm; left USL distance: 5.0 mm; range: 0-20.0 mm). Although the MCP was 3.3 mm (range: 2.5-4.0 mm) left and lateral to the midsagittal line, the right IHP was closer to the MCP (mean distance: 19.6 mm; range: 13.0-25.0 mm) than the left one (mean distance: 20.2 mm; range: 15.0-26.0 mm). Conclusions: Distances between the right IHP and the MSP, MCP, and ipsilateral USL, are shorter compared to these associated to the left IHP. What is new?: Right autonomic pelvic plexus is closer to the midline planes and the ipsilateral USL. These anatomical relationships may be greatly helpful for pelvic surgeon while facing retroperitoneal pelvic surgery and looking for a nerve-sparing approach.

Automated three-dimensional coded contrast imaging hysterosalpingo-contrast sonography: feasibility in office tubal patency testing.

OBJECTIVE: To evaluate the feasibility of transvaginal hysterosalpingo-contrast sonography (HyCoSy) with new automated three-dimensional coded contrast imaging (3D-CCI) software in the evaluation of tubal patency and visualization of tubal course. METHODS: Patients undergoing HyCoSy with automated 3D-CCI software were evaluated prospectively. First, to evaluate the feasibility of 3D visualization of tubal course, we performed consecutive volume acquisitions while injecting SonoVue contrast agent. We then performed conventional two-dimensional (2D) real-time HyCoSy to confirm tubal patency status by detection of saline and air bubbles moving through the Fallopian tubes and around the ovaries. We also evaluated visualization with CCI of the contrast agent around the ovaries, side effects and pain during and after the procedure, by visual analog scale (VAS) (ranging from 0 to 10, with 0 corresponding to no pain and 10 corresponding to maximum pain). RESULTS: A total of 126 patients (252 tubes) underwent 3D-CCI HyCoSy followed by 2D real-time HyCoSy. According to the final 2D real-time evaluation, bilateral tubal patency was observed in 111 patients, bilateral tubal occlusion in four patients and unilateral tubal patency in 11 patients. The concordance rate for tubal patency status between the first 3D volume acquisition and the final 2D real-time evaluation was 84% and that between the second 3D volume acquisition and the final 2D real-time evaluation was 97%. A pain score >5 on VAS was recorded in 58% of patients during the procedure, but a pain score ≤ 5 was recorded in 85.7% of patients immediately after the procedure. CONCLUSIONS: HyCoSy with automated 3D-CCI technology retains the advantages of conventional 2D HyCoSy while overcoming the disadvantages. 2D HyCoSy is highly observer-dependent and is only accurate in the hands of experienced investigators; by obtaining a volume of the uterus and tubes, automated 3D volume acquisition permits visualization of the tubes in the coronal view and of the tubal course in 3D space, and should allow less experienced operators to evaluate tubal patency status relatively easily.

'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.

Adenomyosis: three-dimensional sonographic findings of the junctional zone and correlation with histology.

OBJECTIVE: To correlate with histopathological features the adenomyosis-induced morphological alterations of the outer myometrium and the inner myometrium ('junctional zone', JZ) detectable on two- (2D) and three-dimensional (3D) transvaginal ultrasound imaging (TVS), and to evaluate their diagnostic accuracy for adenomyosis. METHODS: Premenopausal patients scheduled for hysterectomy for benign pathology were enrolled in this prospective study. Before hysterectomy all patients underwent detailed 2D-TVS and 3D volume acquisition of the entire uterus. The major sonographic signs of adenomyosis were noted. On the multiplanar coronal and longitudinal views obtained by 3D-TVS we measured the maximum and minimum JZ thickness from the basal endometrium to the internal layer of the outer myometrium (JZmax, JZmin), the difference between them (JZdif = JZmax - JZmin) and the ratio JZmax/total maximum myometrial thickness. Results of these examinations were correlated blindly to the presence of adenomyosis on histological specimens. RESULTS: A total of 72 premenopausal patients underwent 2D- and 3D-TVS before hysterectomy. The histological prevalence of adenomyosis was 44.4% (32/72 patients). In diagnosing adenomyosis, the presence of myometrial cysts was the most specific 2D-TVS feature (specificity, 98%; accuracy, 78%) and heterogeneous myometrium was the most sensitive (sensitivity, 88%; accuracy, 75%). The 3D-TVS markers JZdif ≥ 4 mm and JZ infiltration and distortion had high sensitivity (88%) and the best accuracy (85% and 82%, respectively). For 2D-TVS and 3D-TVS, respectively, the overall accuracy for diagnosis of adenomyosis was 83% and 89%, the sensitivity was 75% and 91%, the specificity was 90% and 88%, the positive predictive value was 86% and 85% and the negative predictive value was 82% and 92%. CONCLUSIONS: The coronal section of the uterus obtained by 3D-TVS permits accurate evaluation and measurement of the JZ, and its alteration has good diagnostic accuracy for adenomyosis.

Cervical ripening prior to hysteroscopy: is the application of misoprostol useful?

Cervical dilatation has to be considered a fundamental step in operative hysteroscopy. Different methods are used to facilitate cervical dilatation. The aim of this review is to evaluate the efficacy of Misoprostol in cervical ripening prior to operative hysteroscopy through the evaluation of published studies. Initially designed for the treatment of peptic ulcers caused by non-steroidal anti-inflammatory drugs, misoprostol, a prostaglandin E1 analogue, is commonly used for medical abortion in the first and second trimesters, cervical priming before vacuum aspiration or dilation and curettage, induction of labor, and the prevention and treatment of postpartum hemorrhage. Misoprostol was licensed for oral administration, but a large number of clinical studies have reported that vaginal administration is more effective in cervical ripening. Misoprostol is effective in inducing an adequate cervical dilatation prior to an operative hysteroscopy. Vaginal administration could be necessary for all conditions where cervical ripening is difficult to perform. Patients given GnRH analogue therapy before hysteroscopy may benefit from the application of Misoprostol. However, its use in postmenopausal patients may not be efficacious. As far as the application of Misoprostol prior to diagnostic hysteroscopy is concerned, the number of patients that may find an advantage in the treatment is probably very small. Misoprostol has some important advantages, such as easy application, very low price, and greater acceptability by doctors and patients.

[Prevention of postoperative abdominal adhesions in gynecological surgery. Consensus paper of an Italian gynecologists' task force on adhesions]. / Aderenze addominali postoperatorie e loro prevenzione in chirurgia ginecologica. Documento di consenso si una "task force" di ginecologi italiani sulle aderenze.

Adhesions are the most frequent complication of abdominopelvic surgery, causing important short- and long-term problems, including infertility, chronic pelvic pain and a lifetime risk of small bowel obstruction. They also complicate future surgery with considerable morbidity and expense, and an important mortality risk. They pose serious quality of life issues for many patients with associated social and healthcare costs. Despite advances in surgical techniques, the healthcare burden of adhesion-related complications has not changed in recent years. Adhesiolysis remains the main treatment although adhesions reform in most patients. There is rising evidence, however, that surgeons can take important steps to reduce the impact of adhesions. A task force of Italian gynecologists with a specialist interest in adhesions having reviewed the current evidence on adhesions and considered the opportunities to reduce adhesions in Italy, have approved a collective consensus position. This consensus paper provides a comprehensive overview of adhesions and their consequences and practical proposals for actions that gynecological surgeons in Italy should take. As well as improvements in surgical technique, developments in adhesion-reduction strategies and new agents offer a realistic possibility of reducing adhesion formation and improving outcomes for patients. They should be adopted particularly in high risk surgery and in patients with adhesiogenic conditions. Patients also need to be better informed of the risks of adhesions.