Benign descriptors and ADNEX in two-step strategy to estimate risk of malignancy in ovarian tumors: retrospective validation in IOTA5 multicenter cohort.

OBJECTIVE: Previous work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. METHODS: This was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. RESULTS: A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). CONCLUSION: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Typical ultrasound features of various endometrial pathologies described using International Endometrial Tumor Analysis (IETA) terminology in women with abnormal uterine bleeding.

OBJECTIVE: To describe the ultrasound features of different endometrial and other intracavitary pathologies inpre- and postmenopausal women presenting with abnormal uterine bleeding, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective observational multicenter study of consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler and fluid-instillation sonography were performed. Endometrial sampling was performed according to each center's local protocol. The histological endpoints were cancer, atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (EIN), endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma and other. For fluid-instillation sonography, the histological endpoints were endometrial polyp, intracavitary leiomyoma and cancer. For each histological endpoint, we report typical ultrasound features using the IETA terminology. RESULTS: The database consisted of 2856 consecutive women presenting with abnormal uterine bleeding. Unenhanced sonography with color Doppler was performed in all cases and fluid-instillation sonography in 1857. In 2216 women, endometrial histology was available, and these comprised the study population. Median age was 49 years (range, 19-92 years), median parity was 2 (range, 0-10) and median body mass index was 24.9 kg/m2 (range, 16.0-72.1 kg/m2 ). Of the study population, 843 (38.0%) women were postmenopausal. Endometrial polyps were diagnosed in 751 (33.9%) women, intracavitary leiomyomas in 223 (10.1%) and endometrial cancer in 137 (6.2%). None (0% (95% CI, 0.0-5.5%)) of the 66 women with endometrial thickness < 3 mm had endometrial cancer or atypical hyperplasia/EIN. Endometrial cancer or atypical hyperplasia/EIN was found in three of 283 (1.1% (95% CI, 0.4-3.1%)) endometria with a three-layer pattern, in three of 459 (0.7% (95% CI, 0.2-1.9%)) endometria with a linear endometrial midline and in five of 337 (1.5% (95% CI, 0.6-3.4%)) cases with a single vessel without branching on unenhanced ultrasound. CONCLUSIONS: The typical ultrasound features of endometrial cancer, polyps, hyperplasia and atrophy and intracavitary leiomyomas, are described using the IETA terminology. The detection of some easy-to-assess IETA features (i.e. endometrial thickness < 3 mm, three-layer pattern, linear midline and single vessel without branching) makes endometrial cancer unlikely. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Laparoscopic management of a second trimester ruptured spontaneous heterotopic tubal pregnancy mimicking ovarian tumour, a case report.

Background: Laparoscopic surgery in the second trimester of pregnancy is a high risk and demanding operation. Especially when dealing with adnexal pathology, the surgeon should balance between the effort to establish adequate visualisation of the operating field with minimal uterine manipulation and use of energy application to avoid any potential adverse effects on the intrauterine pregnancy. Objective: The video shows laparoscopic surgery performed in the second trimester of pregnancy and highlights modifications to technique to ensure safety. Materials and Methods: We present a case report of spontaneous heterotopic tubal pregnancy that mimicked an ovarian tumour and was managed surgically with a laparoscopy in the second trimester. During surgery, a previously ruptured left tubal pregnancy (? ectopic) was the cause for a concealed hematoma in the pouch of Douglas, misdiagnosed as ovarian tumour. This is one of the few cases of heterotopic pregnancy treated by laparoscopy in the second trimester of pregnancy. Results: The patient was discharged the day 2 post-operatively, the intrauterine pregnancy progressed, and the patient delivered with a planned caesarean section on the 38th week. Conclusions: Laparoscopic surgery, with adjustments, is a safe and effective method to manage adnexal pathology during a second trimester pregnancy.

Imaging of gynecological disease (6): clinical and ultrasound characteristics of ovarian dysgerminoma.

OBJECTIVES: To describe the clinical history and ultrasound findings in patients with ovarian dysgerminoma. METHODS: This was a retrospective study of patients with a histological diagnosis of ovarian dysgerminoma who had undergone preoperative ultrasound examination. The patients were identified from the databases of 11 ultrasound centers. The tumors were described by the principal investigator at each contributing center on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, three authors reviewed all available electronic ultrasound images (gray-scale images and color/power Doppler images were available for 18 patients and 14 patients, respectively) and described them using subjective evaluation of gray-scale and color Doppler ultrasound findings (here called pattern recognition). RESULTS: Twenty-one patients with ovarian dysgerminoma were identified (including one woman with bilateral masses). Twenty patients had a primary ovarian dysgerminoma (including the one with bilateral masses) and one patient had a recurrence of dysgerminoma in her retained ovary. One of the 21 patients was pregnant. All tumors except one were pure dysgerminomas, one being a mixed germinal cell tumor with 30% dysgerminoma component. Median age was 20 (range, 16-31) years. Information on clinical symptoms was available for 18 patients. In four patients, the tumor was detected incidentally, whereas 14 patients presented with one or more of the following symptoms: acute pain (n = 4), chronic pain (n = 8), bloating (n = 8), menstrual disorders (n = 5) and infertility problems (n = 1). One (5%) patient had ascites. Using the IOTA terms and definitions, all but one dysgerminoma were moderately (43%) or very well (50%) vascularized solid tumors. One tumor was multilocular-solid. According to pattern recognition, most dysgerminomas were highly vascularized, purely solid tumors with heterogeneous internal echogenicity divided into several lobules, had a smooth and sometimes lobulated contour and were well-defined relative to the surrounding organs. CONCLUSION: The ultrasound finding of a highly vascularized, large, solid, lobulated adnexal mass with irregular internal echogenicity in a woman 20-30 years old should raise the suspicion of ovarian dysgerminoma.

Lidocaine does not reduce pain perception during gel instillation sonography or subsequent office hysteroscopy: results of a randomized trial.

BACKGROUND: To evaluate if the addition of lidocaine to the gel used for gel infusion sonohysterography (GIS) reduces pain experienced during GIS or subsequent hysteroscopy. METHODS: A total of 142 consecutive patients were randomized using computer-generated random integers. In 79 patients, GIS was performed with a gel containing lidocaine (Instillagel®) and in 63 patients the gel did not contain lidocaine (Endosgel®). Immediately after GIS, 132 patients (94%) underwent office hysteroscopy. The women were asked to fill in a questionnaire including a 100-mm visual analogue scale (VAS) score after each examination. RESULTS: The mean age (SD) was 50.8 (12.1) years; 58.5% were premenopausal and 15.6% were nulliparous. The median (interquartile range (IR)) VAS score during GIS for all women was 6 (19.5): 8 (21) for the lidocaine group versus 5 (18.2) for those who received gel without lidocaine. The median (IR) VAS scores during hysteroscopy in the total group, the Instillagel group and the Endosgel group were 15.5 (43.2), 24 (35) and 9 (52), respectively. None of the differences were statistically significant. CONCLUSION: The addition of lidocaine to the gel used either for GIS or prior to office hysteroscopy does not reduce the procedure-related pain.

A scoring system to differentiate malignant from benign masses in specific ultrasound-based subgroups of adnexal tumors.

OBJECTIVE: To investigate if the prediction of malignant adnexal masses can be improved by considering different ultrasound-based subgroups of tumors and constructing a scoring system for each subgroup instead of using a risk estimation model applicable to all tumors. METHODS: We used a multicenter database of 1573 patients with at least one persistent adnexal mass. The masses were categorized into four subgroups based on their ultrasound appearance: (1) unilocular cyst; (2) multilocular cyst; (3) presence of a solid component but no papillation; and (4) presence of papillation. For each of the four subgroups a scoring system to predict malignancy was developed in a development set consisting of 754 patients in total (respective numbers of patients: (1) 228; (2) 143; (3) 183; and (4) 200). The subgroup scoring system was then tested in 312 patients and prospectively validated in 507 patients. The sensitivity and specificity, with regard to the prediction of malignancy, of the scoring system were compared with that of the subjective evaluation of ultrasound images by an experienced examiner (pattern recognition) and with that of a published logistic regression (LR) model for the calculation of risk of malignancy in adnexal masses. The gold standard was the pathological classification of the mass as benign or malignant (borderline, primary invasive, or metastatic). RESULTS: In the prospective validation set, the sensitivity of pattern recognition, the LR model and the subgroup scoring system was 90% (129/143), 95% (136/143) and 88% (126/143), respectively, and the specificity was 93% (338/364), 74% (270/364) and 90% (329/364), respectively. CONCLUSIONS: In the hands of experienced ultrasound examiners, the subgroup scoring system for diagnosing malignancy has a performance that is similar to that of pattern recognition, the latter method being the best diagnostic method currently available. The scoring system is less sensitive but more specific than the LR model.

Imaging of gynecological disease (3): clinical and ultrasound characteristics of granulosa cell tumors of the ovary.

OBJECTIVES: To describe the clinical and ultrasound characteristics of granulosa cell tumors (GCTs) of the ovary, and to define the ultrasound appearance of GCTs based on pattern recognition. METHODS: Databases of four gynecological ultrasound centers were searched to identify patients with histologically proven GCTs who had undergone a standard preoperative ultrasound examination. RESULTS: A total of 23 women with confirmed GCT were identified. Twelve (52%) women were postmenopausal, nine (39%) were of fertile age and two (9%) were prepubertal. Clinical symptoms were abdominal distension (7/23, 30%), pain (5/23, 22%) and irregular vaginal bleeding (6/23, 26%). Seven patients (30%) were asymptomatic. Endometrial pathology was found in 54% (7/13) of the patients from whom endometrial biopsies were taken. On ultrasound scan 12/23 (52%) masses were multilocular-solid, 9/23 (39%) were purely solid, one mass (4%) was unilocular-solid and one mass was multilocular (4%). Multilocular and multilocular-solid cysts typically contained large numbers of small locules (> 10). The echogenicity of the cyst content was most often mixed (6/16, 38%) or low level (7/16, 44%). Papillary projections were found in only four women (17%). The GCTs were large tumors with a median largest diameter of 102 (range, 37-242) mm and manifested moderate or high color content at color Doppler examination (color score 3 in 13/23 tumors (57%); color score 4 in 8/23 tumors (35%)). CONCLUSIONS: At ultrasound examination, most GCTs are large multilocular-solid masses with a large number of locules, or solid tumors with heterogeneous echogenicity of the solid tissue. Hemorrhagic components are common and increased vascularity is demonstrated at color/power Doppler ultrasound examination. The hyperestrogenic state that is created by the tumor often causes endometrial pathology with bleeding problems as a typical associated symptom.

Pain experienced during transvaginal ultrasound, saline contrast sonohysterography, hysteroscopy and office sampling: a comparative study.

OBJECTIVE: To evaluate and compare the pain experienced by women during transvaginal ultrasound, saline contrast sonohysterography (SCSH), diagnostic hysteroscopy and office sampling. METHODS: This was a descriptive study of 402 consecutive patients presenting at a 'one-stop' Bleeding Clinic between October 2004 and November 2006. Thirty-nine percent of the patients were postmenopausal. The patients underwent the following examinations transvaginally: first ultrasound with color Doppler, second SCSH, third diagnostic hysteroscopy and fourth endometrial biopsy. After completion of the examinations the patients were asked to complete a questionnaire including a visual analog scale (VAS) about their subjective appreciation of all four examinations. Two-hundred and ninety-three (72%) patients returned the questionnaire. RESULTS: The median (range) VAS scores for transvaginal ultrasound, SCSH, diagnostic hysteroscopy and endometrial sampling were 1.0 (0-8.1), 2.2 (0-10), 2.7 (0-10) and 5.1 (0-10), respectively (P < 0.0001). The patients' answers to the other questions about the pain experienced, including comparison with other minor procedures such as venous blood sampling, were all concordant with the VAS scores. CONCLUSIONS: Transvaginal ultrasound was the procedure best accepted, followed by SCSH, hysteroscopy and endometrial sampling. These results suggest that patients would prefer SCSH over hysteroscopy as an initial diagnostic approach in the evaluation of abnormal uterine bleeding.

In vitro effects of endothelin-1 on the contractility of myometrium obtained from pre- and postmenopausal women.

This study was conducted to evaluate the responsiveness of human nonpregnant myometrium to endothelin 1 (ET1) (10(-10) M-10(-6 )M) and KCl (80 mM) in relation to the hormonal profile of the women, who were allocated into three groups: group 1, premenopausal follicular phase, n=14, group 2, premenopausal luteal phase, n=20, and group 3, postmenopausal women, n=12. At a concentration of 10(-6 )M, ET1 in both groups 1 and 2 induced very low ripples of high frequency (group 1: 80+/-14%, n=5, group 2: 314+/-63%, n=11; P<0.05 compared with the pretreatment frequency) which lasted significantly longer in group 2 (29+/-2 min, n=10, P<0.05) than in group 1 (20+/-2 min, n=5), increasing the basal tone (group 1: 57.9+/-6%, n=5, group 2: 64.4+/-4%, n=6), the amplitude of myometrial contractility (group 1: 1.2+/-0.07 g, n=5, group 2: 1.6+/-0.1 g, n=7, P<0.05) and the area under the contractility curve (AUC; group 1: 8.4+/-1.1 gxmin, n=6, group 2: 11.9+/-1.6 g x min, n=11). In group 3, ET1 (10(-6 )M) created a sustained long-lasting contraction (initial phase: 43+/-6 min, n=6) characterized by the complete obliteration of spontaneous contractility with no ripples at all, and increasing significantly (P<0.05) the amplitude of myometrial contractility (2.8+/-0.5 g, n=6), the AUC (24.7+/-3.3 g x min, n=6), as well as the basal tone (183.6+/-21%, n=6) compared with the two premenopausal groups. In all three groups KCl exposure induced an initial rise (mean amplitude value: 1.1 g) followed by a relaxation phase to the primal baseline level (mean duration value: 12 min). Addition of ET1 (10(-6 )M) to KCl (80 mM) induced a similar pattern of contractility to that evoked by ET1 alone which, compared with KCl alone lasted significantly longer (P<0.05) in all three groups (group 1: 20+/-2 min, n=6; group 2: 23+/-2 min, n=6; group 3: 35+/-3 min, n=5). In group 3, the percentage change in basal tone was significantly smaller following KCl than after the combination of KCl plus ET1 (149+/-16%, n=5; P<0.01), indicating a different mechanism of contractility between KCl and ET1. These results demonstrate for the first time differences in myometrial response to ET1 between pre- and postmenopausal women. It is suggested that KCl and ET1 affect uterine contractility through different mechanisms and that ovarian steroids may play a regulatory role in human uterine responsiveness to ET1.

Leptin in pregnancy.

Leptin is a 16-kDa polypeptide, encoded in humans by the LEP gene. This protein is probably involved in the regulation of ovarian function, oocyte maturation and embryo development, and in the implantation process. During pregnancy, leptin is produced in the placenta; its values increase in the maternal blood particularly in the second trimester and decline postpartum. Leptin levels may be abnormally high in pregnancies complicated by conditions such as diabetes mellitus and pre-eclampsia. The role of leptin in fetal physiology has not been clarified, although cord blood values correlate significantly with birth weight. It is expected that further research will provide new insight into the physiological importance of leptin in the pregnant woman and fetus.

A thin and regular endometrium on ultrasound is very unlikely in patients with endometrial malignancy.

OBJECTIVE: To evaluate the clinical and sonographic features in patients with endometrial malignancy in whom endometrial thickness on ultrasound examination had been recorded in our database to be < 5 mm. METHODS: This was a retrospective observational study on 187 consecutive patients diagnosed with endometrial malignancy in whom an ultrasound evaluation of the endometrium had been performed in our institution. The characteristics of those patients presenting with an endometrial thickness < 5 mm were analyzed. RESULTS: The median endometrial thickness was 15 mm: 12 mm for the women who underwent endometrial sampling before ultrasound examination vs. 17 mm in those who did not (P = 0.0086). In 13 women (6.9%), the endometrial thickness recorded in our database was < 5 mm. In 12 of these the measurement was compromised in some way: nine of these patients had undergone endometrial sampling (Pipelle biopsy in one and dilatation and curettage in eight patients) before the ultrasound examination, in two cases, focal malignant lesions were not included in the recorded endometrial thickness and in one, the endometrial thickness was visualized poorly due to myometrial distortion. In only one case was was the endometrium correctly measured to be < 5 mm; this woman had diffuse uterine and endometrial metastases of a breast cancer. CONCLUSIONS: A thin and regular endometrial line is very reliable for the exclusion of endometrial carcinoma. The suspicion of focal lesions as well as incomplete visualization of the endometrium on sonography should be considered abnormal. Recently performed endometrial sampling makes measurement of the endometrial thickness unreliable.

In vitro responsiveness of human post-menopausal myometrium to endothelin-1 and ovarian steroids.

It has been shown in vitro that endothelin 1 (ET1) differentially affects the human myometrial contractility according to the hormonal profile of women. Our purpose was to test the hypothesis that ovarian steroids influence the ET1 induced myometrial contractility. We performed three types of experiments. Myometrial tissues were exposed to 17beta-oestradiol (E), progesterone (P), E plus P (E+P) in concentrations 10(-10)M, 10(-8)M, 10(-7)M, 10(-6)M and 10(-4)M (Type I), ET1 in concentrations 10(-10)M, 10(-9)M, 10(-8)M, 10(-7)M and 10(-6)M (Type II) and E+ET1, P+ET1 and E+P+ET1 in concentrations ranging from 10(-10)M to 10(-6)M (Type III). Tissue exposure to E, P and E+P did not significantly alter the pattern of spontaneous myometrial motility. ET1 (10(-6)M) induced a sustained long-lasting contraction, the initial part of which lasted 34 +/- 4 min, elevating the initial baseline by 190 +/- 20%. This was followed by ripples of gradually increasing amplitude with no regular contractions up to the end of the period of observation (120 min). Addition of P or E+P to ET1 markedly restricted (p<0.05) the elevation of initial baseline (P+ET1: 68 +/- 8%, P+E+ET1: 67 +/- 8%), and significantly shortened (p<0.01) the duration of the alterations (P+ET1: 21 +/- 3 min, P+E+ET1: 26 +/- 3 min). These results demonstrate the lack of any significant effect of E and P or their combinations on the pattern of spontaneous myometrial motility in post-menopausal women. However, P alone or in combination with E exerted an inhibitory action on ET1 -induced contractility on human post-menopausal myometrium. The physiological significance of these findings remains to be clarified.

Alternate day and daily administration of GnRH antagonist may prevent premature luteinization to a similar extent during FSH treatment.

BACKGROUND: This randomized controlled trial was designed to evaluate whether a GnRH antagonist given every other day could prevent premature luteinization in women undergoing IVF/ICSI treatment. METHODS: A total of 73 women receiving ovulation stimulation IVF cycles with recombinant FSH were allocated randomly on cycle day 7 to GnRH antagonist ganirelix in multiple doses (0.25 mg each), either daily (n = 37 women, group 1) or every other day (n = 36 women, group 2) until the day of HCG administration. RESULTS: Serum FSH, LH, estradiol and progesterone values showed similar trends in the two groups. During FSH stimulation, 13 (35%) of the women in group 1 had premature LH rises (> or = 10 IU/l) of which eight (22%) were after the start of antagonist administration. In group 2 there were 14 (39%) LH rises during FSH stimulation of which 10 (28%) were after the start of antagonist administration. Luteinization (serum progesterone >2 ng/ml) occurred in only one woman in each group overall (3%). A significantly smaller total dose of the antagonist was used in group 2 than in group 1 (P < 0.001). The study did not have power to evaluate differences in total dose of FSH, number of oocytes recovered and clinical pregnancy rate, all of which appeared similar in the two groups. CONCLUSIONS: Whether alternate day is as effective as daily administration of ganirelix in preventing premature luteinization should be addressed in a non-inferiority trial powered to evaluate live birth rate.