Validation of ultrasound strategies to assess tumor extension and to predict high-risk endometrial cancer in women from the prospective IETA (International Endometrial Tumor Analysis)-4 cohort.

OBJECTIVES: To compare the performance of ultrasound measurements and subjective ultrasound assessment (SA) in detecting deep myometrial invasion (MI) and cervical stromal invasion (CSI) in women with endometrial cancer, overall and according to whether they had low- or high-grade disease separately, and to validate published measurement cut-offs and prediction models to identify MI, CSI and high-risk disease (Grade-3 endometrioid or non-endometrioid cancer and/or deep MI and/or CSI). METHODS: The study comprised 1538 patients with endometrial cancer from the International Endometrial Tumor Analysis (IETA)-4 prospective multicenter study, who underwent standardized expert transvaginal ultrasound examination. SA and ultrasound measurements were used to predict deep MI and CSI. We assessed the diagnostic accuracy of the tumor/uterine anteroposterior (AP) diameter ratio for detecting deep MI and that of the distance from the lower margin of the tumor to the outer cervical os (Dist-OCO) for detecting CSI. We also validated two two-step strategies for the prediction of high-risk cancer; in the first step, biopsy-confirmed Grade-3 endometrioid or mucinous or non-endometrioid cancers were classified as high-risk cancer, while the second step encompassed the application of a mathematical model to classify the remaining tumors. The 'subjective prediction model' included biopsy grade (Grade 1 vs Grade 2) and subjective assessment of deep MI or CSI (presence or absence) as variables, while the 'objective prediction model' included biopsy grade (Grade 1 vs Grade 2) and minimal tumor-free margin. The predictive performance of the two two-step strategies was compared with that of simply classifying patients as high risk if either deep MI or CSI was suspected based on SA or if biopsy showed Grade-3 endometrioid or mucinous or non-endometrioid histotype (i.e. combining SA with biopsy grade). Histological assessment from hysterectomy was considered the reference standard. RESULTS: In 1275 patients with measurable lesions, the sensitivity and specificity of SA for detecting deep MI was 70% and 80%, respectively, in patients with a Grade-1 or -2 endometrioid or mucinous tumor vs 76% and 64% in patients with a Grade-3 endometrioid or mucinous or a non-endometrioid tumor. The corresponding values for the detection of CSI were 51% and 94% vs 50% and 91%. Tumor AP diameter and tumor/uterine AP diameter ratio showed the best performance for predicting deep MI (area under the receiver-operating characteristics curve (AUC) of 0.76 and 0.77, respectively), and Dist-OCO had the best performance for predicting CSI (AUC, 0.72). The proportion of patients classified correctly as having high-risk cancer was 80% when simply combining SA with biopsy grade vs 80% and 74% when using the subjective and objective two-step strategies, respectively. The subjective and objective models had an AUC of 0.76 and 0.75, respectively, when applied to Grade-1 and -2 endometrioid tumors. CONCLUSIONS: In the hands of experienced ultrasound examiners, SA was superior to ultrasound measurements for the prediction of deep MI and CSI of endometrial cancer, especially in patients with a Grade-1 or -2 tumor. The mathematical models for the prediction of high-risk cancer performed as expected. The best strategies for predicting high-risk endometrial cancer were combining SA with biopsy grade and the subjective two-step strategy, both having an accuracy of 80%. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasonographic soft markers for detection of rectosigmoid deep endometriosis.

OBJECTIVES: The aim of this study was to evaluate the use of ultrasound (US) soft markers as a first-line imaging tool to raise suspicion of rectosigmoid (RS) involvement in women suspected of having deep endometriosis. METHODS: We included in this prospective observational study all patients with clinical suspicion of deep endometriosis who underwent diagnostic transvaginal US evaluation at our unit from January 2016 to February 2017. Several US soft markers were evaluated for prediction of RS involvement (presence of US signs of uterine adenomyosis, presence of an endometrioma, adhesion of the ovary to the uterus (reduced ovarian mobility), presence of 'kissing ovaries' (KO) and absence of the 'sliding sign'), using as the gold standard expert US examination for the presence of RS endometriosis. RESULTS: Included were 333 patients with clinical suspicion of deep endometriosis. Of these, 106 had an US diagnosis of RS endometriosis by an expert. The only significant variables found in the prediction model were absence of the sliding sign (odds ratio (OR), 13.95; 95% CI, 7.7-25.3), presence of KO (OR, 22.5; 95% CI, 4.1-124.0) and the interaction between these two variables (OR, 0.03; 95% CI, 0.004-0.28). Regarding their interaction, RS endometriosis was present when KO was absent and the sliding sign was present in 10% (19/190) of cases, when both KO and the sliding sign were present in 71.4% (5/7) of cases, when both KO and the sliding sign were absent in 60.8% (76/125) of cases and when KO was present and the sliding sign was absent in 54.5% (6/11) of cases. Thus, when the sliding sign was absent and/or KO was present, transvaginal US showed a specificity of 75% (95% CI, 69-80%) and a sensitivity of 82% (95% CI, 73-88%). CONCLUSIONS: US findings of absence of the sliding sign and/or presence of KO in patients with clinical suspicion of endometriosis should raise suspicion of RS involvement and indicate referral for expert US examination, with a low rate of false-negative diagnosis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Learning curve for ultrasonographic diagnosis of deep infiltrating endometriosis using structured offline training program.

OBJECTIVE: To assess the learning curves of trainees during a structured offline/hands-on training program for the ultrasonographic diagnosis of deep infiltrating endometriosis (DIE). METHODS: Four trainees (all Ob/Gyn postgraduates with at least 5 years' experience in ultrasonography in obstetrics and gynecology, but with no experience of sonographic examination of DIE) participated in the study. They underwent a 2-week training program with a single trainer. Day 1 was devoted to theoretical issues and guided offline analysis of 10 three-dimensional ultrasound volumes. During the following days, four sessions of real-time sonographic examinations were performed in a DIE referral center ultrasound unit. In between these sessions, the trainees analyzed four datasets offline, each containing 25 volumes. At the end of each set, misinterpreted volumes were reassessed with the trainer. Presence or absence of DIE at surgery was considered the gold standard. The trainees' learning process was evaluated by learning-curve cumulative summation (LC-CUSUM) and the deviations of the trainees' level of performance at the control stage was assessed by CUSUM (standard CUSUM), for different locations of DIE. RESULTS: The trainees reached competence after an average of 17 (range, 14-21) evaluations for bladder, 40 (range, 30-60) for rectosigmoid, 25 (range, 14-34) for forniceal, 44 (range, 25-66) for uterosacral ligament (USL) and 21 (range, 14-43) for rectovaginal septum (RVS) locations of DIE, and then kept the process under control, with error levels of less than 4.5% until the end of the test. The overall accuracy for each trainee in diagnosis of DIE at the different locations ranged from 0.91 to 0.98 for bladder DIE, from 0.80 to 0.94 for rectosigmoid DIE, from 0.90 to 0.94 for forniceal DIE, from 0.79 to 0.82 for USL DIE and from 0.89 to 0.98 for RVS DIE. CONCLUSIONS: The suggested 2-week training program, based on a mixture of offline and live scanning sessions, is feasible and apparently provides effective training for the ultrasonographic diagnosis of DIE. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

First case of prophylactic salpingectomy with single port access laparoscopy and a new diode laser in a woman with BRCA mutation.

•Single port access laparoscopy may be suggested for prophylactic salpingectomy in BRCA carriers.•Diode laser salpingectomy could preserve ovarian function as it can cut and coagulate with extreme precision and minimal thermal damage.

CD10 in the developing human kidney: immunoreactivity and possible role in renal embryogenesis.

CD10 was first identified in tumor cells of acute lymphoblastic leukemia. Most studies on CD10 expression have dealt with tumor pathology. Since no data are available for specific role in the fetal kidney, this study aimed at investigating CD10 expression during the different phases of renal embryogenesis. To this end, the expression of CD10 was evaluated in the kidney of two human fetus and in three newborns. In both fetuses, immunostaining for CD10 was compartmentalized and mainly concentrated in the mid-deep cortex. Reactivity for CD10 was stronger in the glomerular epithelium, in proximal tubules and in metanephric mesenchymal cells. At 25 weeks of gestation, CD10 was also detected in the subcapsular regions, including some pretubular aggregates of cap mesenchymal cells and renal vesicles. At 34 weeks of gestation, we observed an increased immunoreactivity for CD10 in visceral and parietal glomerular epithelium. At 39 weeks of gestation, CD10 was also expressed in the collecting tubules and in the Henle loops. Our data show a strong expression of CD10 in all stage of human kidney development, characterized by dynamic changes and support the hypothesis that CD10 plays a relevant role in renal embryogenesis.

[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.

Determinants of adenomyosis in women who underwent hysterectomy for benign gynecological conditions: results from a prospective multicentric study in Italy.

OBJECTIVE: We conducted a cross-sectional study on the frequency and risk factors for adenomyosis in women who underwent hysterectomy for benign gynecological conditions. STUDY DESIGN: All women who consecutively underwent hysterectomy during the study period for benign gynecological conditions at 18 gynecological departments were eligible for the study. A total of 820 women entered the study. Pathological data were collected prospectically. RESULTS: Adenomyosis was identified in 231 women (28.2%, 95% confidence interval, CI, 24.6-32.5). The frequency of adenomyosis was similar in women with indication for surgery fibroids/menorrhagia (143 cases, 28.5%) or genital prolapse (69 cases, 28.2%). The rate ratio (RR) of adenomyosis was 1.9 (95% CI 1.2-2.8) in women reporting one or more induced abortions, in comparison with those reporting no induced abortion. Women with adenomyosis reported more frequently dysmenorrhoea and chronic pelvic pain, but not dyspareunia. CONCLUSIONS: This study shows that adenomyosis is common in women who undergo hysterectomy and that it is more frequent among women reporting induced abortions dysmenorrhoea and chronic pelvic pain.

Laparoscopic excision of posterior vaginal fornix in the treatment of patients with deep endometriosis without rectum involvement: surgical treatment and long-term follow-up.

BACKGROUND: The objective of the study is to evaluate the short- and long-term efficacy of complete laparoscopic excision of deep endometriosis, without rectum involvement, with the opening and partial excision of the posterior vaginal fornix. METHODS: Thirty-one patients were included in the study with symptomatic extensive disease including involvement of the cul-de-sac, rectovaginal space and posterior vaginal fornix without rectum involvement. Endoscopic surgery was performed with complete separation of rectovaginal space and in-block resection of the diseased tissue, opening and partial excision of the posterior vaginal fornix and vaginal closure either by laparoscopic or by vaginal route. Patients filled in questionnaires on pain before and 12, 24, 36, 48 and 60 months after surgical treatment. RESULTS: No intraoperative complications were observed; 65% were free of analgesic on post-operative day 2, 38% had total remission of chronic pain and 22% were improved; 38% had total remission of dysmenorrhoea and 22% were improved; 45% had total remission of dyspareunia and 25% were improved. Follow-up improvement of symptoms was statistically significant and was maintained for 5 years without recurrence of the disease or repeated surgery (P < 0.001). CONCLUSION: Complete surgical resection of deep infiltrative endometriosis with excision of the adjacent tissue of the posterior vaginal fornix improves quality of life with persistence of results for long time in patients not responsive to medical treatment.

Reduction of postoperative adhesions with an auto-crosslinked hyaluronan gel in gynaecological laparoscopic surgery: a blinded, controlled, randomized, multicentre study.

BACKGROUND: Following myomectomy, postoperative adhesions occur in many patients with adverse effects on fertility. This study investigated the applicability, safety and efficacy of an auto-crosslinked hyaluronan gel in preventing adhesion formation after laparoscopic myomectomy. METHODS: Fifty-two patients aged 22-42 years, undergoing surgery at four centres, were randomly allocated to receive either the gel or no adhesion prevention. The incidence and severity of postoperative adhesions were assessed laparoscopically after 12-14 weeks in a blinded, scored fashion. The primary efficacy variable was the presence/absence of postoperative adhesions at second-look. RESULTS: A nonsignificantly higher proportion of patients receiving the gel were free from adhesions (13 of 21; 62%) compared with control patients (9 of 22; 41%), with a statistically significant difference between the severity of uterine adhesions at baseline and at second-look (0.3 +/- 0.9 versus 0.8 +/- 1.0, P < 0.05). In subjects undergoing myomectomy without concomitant surgery, the proportion of adhesion-free patients was 8 of 12 (67%) and 4 of 11 (36%) (not significant) in the gel and control groups, respectively, with a significant difference in the mean severity scores (P < 0.05). In subjects without uterine adhesions before myomectomy, 12 of 18 (67%) and 8 of 20 (40%) patients in the gel and control groups, respectively were adhesion-free (not significant), with a significant difference in the severity of uterine adhesions (P = 0.05). CONCLUSIONS: Our results suggest that the auto-crosslinked hyaluronan gel may have a favourable safety profile and efficacious antiadhesive action following laparoscopic myomectomy.

Transvaginal ultrasonography associated with colour Doppler energy in the diagnosis of hydrosalpinx.

The aims of this prospective study were to investigate the accuracy of B-mode transvaginal ultrasonography alone, using the typical finding of the presence of an elongated shaped mass with incomplete septa, in the screening of hydrosalpinx in women undergoing surgery for gynaecological diseases, and to determine the predictive value of this method combined with colour Doppler energy (CDE) imaging evaluation and CA125 concentrations in differentiating hydrosalpinx from other adnexal masses. In the first part of the study, 378 consecutive pre-menopausal non-pregnant women were submitted to transvaginal ultrasonography alone before surgery. In the second part of the study, 256 adnexal masses underwent transvaginal ultrasonography combined with CDE imaging evaluation associated with spectral Doppler analysis and plasma concentrations of CA125. Sensitivity and specificity for the ultrasonographic screening were 84.6 and 99.7% respectively, calculated for each adnexum (n = 756) and 93.3 and 99.6% respectively, calculated for each mass, for differentiating hydrosalpinx from other adnexal masses. The CDE imaging and the evaluation of CA125 plasma concentrations do not seem to increase the accuracy of B-mode transvaginal ultrasonography. Inter- and intra-observer agreement, expressed in terms of k-values, was high (0.87 and 0.93 respectively). In conclusion, transvaginal ultrasonography alone is a useful method of detection of hydrosalpinx.

Effect of multiple follicular development on uterine perfusion in subsequent spontaneous cycles.

OBJECTIVE: To investigate the effect of ovarian hyperstimulation on uterine perfusion during a subsequent natural cycle to evaluate if there is a long-term effect of treatment with gonadotropins. STUDY DESIGN: Thirty-five infertile couples were subjected to three cycles of multiple follicular development. Uterine blood flow was determined during the follicular phase, ovulation and luteal phase of the spontaneous cycle preceding and the one following the stimulated cycles. RESULTS: No significant difference was present among pulsatility index (PI) values in the two cycles. PI values (+/- SD) were 2.05 +/- 0.5, 2.28 +/- 0.4, 2.18 +/- 0.5, 2.13 +/- 0.4 and 2.00 +/- 0.5, respectively, in the pretreatment cycle and 2.32 +/- 0.5, 2.56 +/- 0.6, 2.42 +/- 0.3, 2.37 +/- 0.4 and 2.29 +/- 0.5, respectively, in the posttreatment cycle. An inverse correlation was found between PI values and estradiol in the follicular phase of the first spontaneous cycle. As for radial and subendometrial arteries, no significant difference was present for PI values in the two cycles. CONCLUSION: Multiple follicular development seems not to have a long-term effect on uterine perfusion in the subsequent spontaneous cycle.

The diagnosis of endometriomas using colour Doppler energy imaging.

We studied the role of colour Doppler energy (CDE) (or power Doppler) imaging in the differentiation between endometriomas and other adnexal masses in premenopausal non-pregnant women. A total of 170 consecutive patients with persistent adnexal masses was submitted to B-mode transvaginal ultrasonography associated with CDE imaging evaluation. Plasma concentrations of CA125 were measured before surgery. Using CDE imaging evaluation of vessel distribution, the occurrence of one of the following findings was considered to indicate the likely presence of endometrioma: (i) a round-shaped homogeneous hypoechoic 'tissue' of low-level echoes without papillary proliferations associated with 'poor' vascularization; (ii) a round-shaped homogeneous hypoechoic 'tissue' of low-level echoes with an echogenic portion in which no flow was detected. The overall agreement between the test result and the actual outcome was calculated using the k index. The CDE imaging evaluation was more accurate in the diagnosis of endometriomas compared with B-mode ultrasonography alone (k = 0.88 and 0.80 respectively). According to the logistic regression equation obtained, the probability of the presence of endometrioma varied between a minimum of 1.4% for patients with no risk factors to a maximum of 95.6% for patients with two risk factors (CDE result and value of CA125 >25 IU/ml).

Diagnosis of adnexal malignancies by using color Doppler energy imaging as a secondary test in persistent masses.

The purpose of this prospective study was to compare the accuracy of B-mode transvaginal ultrasonography alone and in combination with color Doppler energy (or power Doppler) imaging in differentiating benign from malignant adnexal masses. A total of 192 consecutive persistent adnexal masses (159 benign, 33 malignant) were studied before surgery by B-mode transvaginal ultrasonography with and without color Doppler energy. In addition, CA-125 plasma levels were determined and spectral Doppler analysis was performed. By color Doppler energy imaging, a mass was considered malignant when arterial flow was visualized in an echogenic portion of a mass defined as malignant by B-mode. Intratumoral arterial blood flow could be readily detected by color Doppler energy imaging in all malignant tumors and in 94% of the benign tumors. The combined use of transvaginal B-mode ultrasonography and color Doppler energy imaging has greater accuracy in the diagnosis of ovarian malignancies than transvaginal ultrasonography alone (value of kappa: 0.81 and 0.63, respectively), reducing the number of false-positive results. The use of spectral Doppler analysis was of limited diagnostic value, with a kappa value of 0.17 for the pulsatility index (< 1) and of 0.41 for the resistance index (< 0.4). Also, the association with CA-125 increased the number of false-negative results. In conclusion, the use of color Doppler energy imaging seems to be a useful secondary test when a mass is suspected to be malignant by B-mode ultrasonography.

Transvaginal ultrasound and computed tomography combined with clinical parameters and CA-125 determinations in the differential diagnosis of persistent ovarian cysts in premenopausal women.

The purpose of this prospective study was to compare the accuracy of computed tomography (CT) and transvaginal ultrasonography in the differential diagnosis of persistent cystic ovarian lesions. The candidates for this study were 161 premenopausal non-pregnant women with an adnexal mass. After a 3-month follow-up, 83 masses persisted and were examined by both techniques before surgery. We also evaluated the CA-125 plasma levels. The CT and ultrasonographic diagnoses were then compared with the histopathological diagnosis. The overall agreement between the test results and the actual outcome was calculated by means of the kappa statistic. Transvaginal ultrasonography has a closer accuracy in the diagnosis of serous cysts and serous cystadenoma, ovarian carcinoma and endometrioma (value of kappa: 0.78, 0.73 and 0.80, respectively) than CT, even if the latter is associated with clinical and biochemical parameters such as patient's age and CA-125 plasma levels. Only in the diagnosis of cystic teratoma, is transvaginal ultrasonography less accurate than CT. In conclusion, in premenopausal women, transvaginal ultrasonography remains a cost-effective method in the diagnosis of most cystic ovarian lesions.

Transvaginal ultrasonography in the diagnosis of pelvic adhesions.

We studied the role of transvaginal ultrasonography and clinical factors in the diagnosis of pelvic adhesions in a population of 139 consecutive pre-menopausal non-pregnant women submitted to diagnostic and/or operative laparoscopy between February 1995 and November 1996. All patients underwent transvaginal ultrasonography and were interviewed within 2 days of their laparoscopy. The ultrasonographic impressions were then compared with the laparoscopic diagnosis. Patients were classified as having tuboperitoneal abnormalities if evidence of fimbrial, peritubal and/or peri-ovarian adhesions was encountered during surgery. The overall agreement between the ultrasound test result and the surgical findings was calculated using the kappa index. The adhesion of the ovary to the uterus, as evaluated by transvaginal ultrasonography, is most accurate in diagnosing pelvic adhesions (kappa = 0.5) in comparison with the other ultrasonographic findings and clinical parameters. According to the logistic regression equation that was obtained, the probability of the presence of pelvic adhesions varied between a minimum of 12% for patients with no risk factors to a maximum of 93% for patients with three risk factors (previous pelvic surgery and transvaginal ultrasound findings of blurring of the margins of the ovary and adhesion of the ovary to the uterus).

Tumor markers and transvaginal ultrasonography in the diagnosis of endometrioma.

OBJECTIVE: To evaluate the accuracy of CA 19.9 plasma levels (with or without CA 125 levels) combined with transvaginal ultrasonography in the differential diagnosis of endometrioma. METHODS: One hundred eighteen consecutive premenopausal nonpregnant women had laparoscopy or laparotomy between November 1994 and November 1995 because of the presence of a persistent adnexal mass. They underwent transvaginal ultrasonography and measurement of CA 19.9 and CA 125 plasma levels within 2 days before surgery. The ultrasonographic impression and the tumor marker values were compared with the histopathologic diagnosis. The overall agreement between the test result and the actual outcome was calculated using the kappa statistic. RESULTS: Transvaginal ultrasonography had a strong agreement between test result and surgery (kappa value 0.84), whereas the combined methods were associated with a lower kappa value (range 0.24-0.80). CONCLUSION: Transvaginal ultrasonography used alone is the most cost-effective method in the preoperative differential diagnosis of endometrioma.

The screening of tubal abnormalities in the infertile couple.

PURPOSE: Our goal was to assess, with a prospective study, the role of hysterosalpingo-contrast sonography (HyCoSy) with an echocontrast agent and transvaginal ultrasonography alone in the evaluation of tubal status. METHODS: Thirty patients were included in the study. These patients underwent an initial plain transvaginal ultrasound examination the day before the HyCoSy. The findings obtained from both examinations were compared with laparoscopic diagnosis, performed in the same menstrual cycle. RESULTS: The kappa values were 0.48 for patency evaluation and 0.67 for the diagnosis of the presence of at least one patent tube, suggesting a good agreement in both cases between HyCoSy and surgery. HyCoSy had a significantly lower sensitivity (50%), but not a significantly higher specificity (75%), than transvaginal ultrasonography alone in the diagnosis of tubal infertility-related abnormalities such as peritubal adhesions. CONCLUSIONS: The study demonstrates that the HyCoSy is a useful test when scheduling the most suitable treatment for infertile couples.