Prediction of non-resectability using the updated Predictive Index Value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study.

BACKGROUND: A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index Value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of non-resectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model). OBJECTIVE: The aim was to demonstrate the non-inferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted (WB DWI)/MRI) in predicting non-resectable tumor (defined as residual disease>1 cm) using the updated PIV model in patients with tubo-ovarian cancer. The agreement between imaging and intraoperative findings as a reference was also calculated. STUDY DESIGN: This was a European prospective multicenter observational study. We included patients with suspected tubo-ovarian carcinoma who underwent preoperative staging and prediction of non-resectability at ultrasound, CT, WB-DWI/MRI and surgical exploration. The predictors of non-resectability were suspicious mesenteric retraction and/or miliary carcinomatosis of the small bowel or if absent, a PIV>8 (updated PIV model). The PIV score ranges from 0 to 12 according to the presence of disease in six predefined intra-abdominal sites (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel serosa/mesentery). The reference standard was surgical outcome, in terms of residual disease>1 cm, assessed by laparoscopy and/or laparotomy. The area under the receiver operating characteristic curve (AUC) to assess the performance of the methods in predicting non-resectability was reported. Concordance between index tests at detection of disease at six predefined sites and intraoperative exploration as reference standard was also calculated using Cohen's kappa. RESULTS: The study was between 2018 and 2022 in five European gynecological oncology centers. Data from 242 patients having both mandatory index tests (ultrasound and CT) were analyzed. 145/242 (59.9%) patients had no macroscopic residual tumor after surgery (R0) (5/145 laparoscopy and 140/145 laparotomy) and 17/242 (7.0%) had residual tumor ≤1cm (R1) (laparotomy). In 80/242 patients (33.1%), the residual tumor was >1 cm (R2), 30 of them underwent laparotomy and maximum surgery was carried out and 50/80 underwent laparoscopy and cytoreduction was not feasible in all of them. After excluding 18/242 (7.4%) patients operated on but not eligible for extensive surgery, the predictive performance of three imaging methods was analyzed in 167 women. The AUCs of all methods in discriminating between resectable and non-resectable tumor was 0.80 for ultrasound, 0.76 for CT, 0.71 for WB-DWI/MRI and 0.90 for surgical exploration. Ultrasound had the highest agreement (Cohen's kappa ranging from 0.59 to 0.79) compared to CT and WB-DWI/MRI to assess all parameters included in the updated PIV model. CONCLUSIONS: Ultrasound showed non-inferiority to CT and to WB-DWI/MRI in discriminating between resectable and non-resectable tumor using the updated PIV model. Ultrasound had the best agreement between imaging and intraoperative findings in the assessment of parameters included in the updated PIV model. Ultrasound is an acceptable method to assess abdominal disease and predict non-resectability in patients with tubo-ovarian cancer in the hands of specially trained ultrasound examiners.

SUCCOR morbidity: complications in minimally invasive versus open radical hysterectomy in early cervical cancer.

OBJECTIVE: The aim of this study was to compare the incidence of intra-operative and post-operative complications in open and minimally invasive radical hysterectomy for patients with early-stage cervical cancer. METHODS: Data were collected from the SUCCOR database of 1272 patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO), 2009) who underwent radical hysterectomy in Europe between January 2013 and December 2014. We reviewed the duration of the surgeries, estimated blood loss, length of hospital stay, intra-operative and post-operative complications. The inclusion criteria were age ≥18 years and histologic type (squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma). Pelvic MRI confirming a tumor diameter ≤4 cm with no parametrial invasion and a pre-operative CT scan, MRI, or positron emission tomography CT demonstrating no extra-cervical metastatic disease were mandatory. Outcomes of interest were any grade >3 adverse events, intra-operative adverse events, post-operative adverse events, length of hospital stay, length of operation, and blood loss. RESULTS: The study included 1156 patients, 633 (54%) in the open surgery group and 523 (46%) in the minimally invasive surgery group. Median age was 46 years (range 18-82), median body mass index 25 kg/m2 (range 15-68), and 1022 (88.3%) patients were considered to have an optimal performance status (ECOG Performance Status 0). The most common histologic tumor type was squamous carcinoma (n=794, 68.7%) and the most frequent FIGO staging was IB1 (n=510, 44.1%). In the minimally invasive surgery group the median duration of surgery was longer (240 vs 187 min, p<0.01), median estimated blood loss was lower (100 vs 300 mL, p<0.01), and median length of hospital stay was shorter (4 vs 7 days, p<0.01) compared with the abdominal surgery group. There was no difference in the overall incidence of intra-operative and post-operative complications between the two groups. Regarding grade I complications, the incidence of vaginal bleeding (2.9% vs 0.6%, p<0.01) and vaginal cuff dehiscence was higher in the minimally invasive surgery group than in the open group (3.3% vs 0.5%, p<0.01). Regarding grade III post-operative complications, bladder dysfunction (1.3% vs 0.2%, p=0.046) and abdominal wall infection (1.1% vs 0%, p=0.018) were more common in the open surgery group than in the minimally invasive surgery group. Ureteral fistula was more frequent in the minimally invasive group than in the open surgery group (1.7% vs 0.5%, p=0.037). CONCLUSION: Our study showed that there was no significant difference in the overall incidence of intra-operative and post-operative complications between minimally invasive radical hysterectomy and the open approach.

The Diagnostic Accuracy of Transvaginal Ultrasound for Detection of Ureteral Involvement in Deep Infiltrating Endometriosis: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study is to determine the accuracy of transvaginal ultrasound (TVU) for the diagnosis of ureteral involvement in women with deep infiltrating endometriosis (DIE). METHODS: The meta-analysis included primary studies comparing the use of TVU for diagnosing endometriotic involvement of the ureter, using laparoscopic surgery and histological diagnosis as the reference standard. Search was performed in several databases (Scopus, Web of Science, and PubMed/MEDLINE). The studies' quality and bias risk were assessed using the Quality Assessment of Diagnostic Accuracy Study-2 (QUADAS-2). Diagnostic performance was estimated by assessing pooled sensitivity and specificity. RESULTS: A total of 496 citations were found. Six articles were ultimately selected for this systematic review and meta-analysis after the inclusion and exclusion criteria were applied. Pooled sensitivity and specificity were 0.81 (95% CI: 0.42-0.96), 1.00 (95% CI: 0.93-1.00). The heterogeneity observed was high for both sensitivity and specificity. Overall risk of bias was low. CONCLUSION: TVU is a valuable tool for the pre-operative identification of ureteral involvement by DIE.

Transvaginal Sonography for the Preoperative Assessment of Parametrial Deep Infiltrating Endometriosis: A Diagnostic Accuracy Study.

OBJECTIVE: The aim of the study was to evaluate the diagnostic accuracy for parametria endometriosis (PE) of transvaginal sonography (TVS) performed following a systematic approach for the assessment of the lateral parametria. DESIGN: A diagnostic accuracy study was employed based on a prospective observational design. PARTICIPANTS: All consecutive patients who underwent laparoscopic surgery for endometriosis between January 2016 and December 2020 were considered. SETTING: The study was conducted at endometriosis referral hospitals. METHODS: We prospectively collected clinical, imaging, and surgical data of all consecutive patients who underwent laparoscopic surgery for endometriosis between January 2016 and December 2020. A standardized technique with a systematic approach for the assessment of the lateral parametria following specific anatomic landmarks was used for the TVS. The diagnostic accuracy for PE in TVS was assessed using the intraoperative and pathologic diagnosis of PE as the gold standard. RESULTS: In 476 patients who underwent surgery, PE was identified in 114 out of 476 patients (23.95%): 91 left and 54 right PE out of 476 surgical procedures were identified (19.12% vs. 11.34%; p = 0.001); bilateral involvement in 27.19% (31/114 patients) cases. The sensitivity of TVS for PE was 90.74% (79.70-96.92%, 95% CI) for the right side and 87.91% (79.40-93.81%, 95% CI) for the left side. The specificity was almost identical for both sides (98.58% vs. 98.18%). For the right parametrium, the positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 63.82 (28.70-141.90, 95% CI) and 0.09 (0.04-0.22, 95% CI), respectively. On the left parametrium, the PLR and NLR were 48.35 (23.12-101.4, 95% CI) and 0.12 (0.07-0.21, 95% CI), respectively. The diagnostic accuracy for right and left PE was 97.69% (95.90-98.84%, 95% CI) and 96.22% (94.04-97.74%, 95% CI), respectively. LIMITATIONS: The principal limit is the high dependence of TVS on the operator experience. Therefore, although a standardized approach following precise definitions of anatomical landmarks was used, we cannot conclude that the observed accuracy of TVS for PE is the same for all sonographers. In this regard, the learning curve was not assessed. In the case of negative TVS for parametrial involvement with an absent intraoperative suspect, a complete dissection of the parametrium was not performed to avoid surgical complications; therefore, cases of minor PE may be missed, underestimating false negatives. CONCLUSIONS: TVS performed following a systematic approach for assessing the lateral parametria seems to have good diagnostic accuracy for PE with large changes in the posttest probability of parametrial involvement based on the TVS evaluation. Considering the clinical and surgical implications of PE, further studies implementing a standardized approach for assessing the parametrium by TVS are recommended to confirm our observations and implement a standardized protocol in clinical practice.

Ultrasound examination, MRI, or ROMA for discriminating between inconclusive adnexal masses as determined by IOTA Simple Rules: a prospective study.

OBJECTIVE: To determine the best second-step approach for discriminating benign from malignant adnexal masses classified as inconclusive by International Ovarian Tumour Analysis Simple Rules (IOTA-SR). METHODS: Single-center prospective study comprising a consecutive series of patients diagnosed as having an adnexal mass classified as inconclusive according to IOTA-SR. All women underwent Risk of Ovarian Malignancy Algorithm (ROMA) analysis, MRI interpreted by a radiologist, and ultrasound examination by a gynecological sonologist. Cases were clinically managed according to the result of the ultrasound expert examination by either serial follow-up for at least 1 year or surgery. Reference standard was histology (patient was submitted to surgery if any of the tests was suspicious) or follow-up (masses with no signs of malignancy after 12 months were considered benign). Diagnostic performance of all three approaches was calculated and compared. Direct cost analysis of the test used was also performed. RESULTS: Eighty-two adnexal masses in 80 women (median age 47.6 years, range 16 to 73 years) were included. Seventeen patients (17 masses) were managed expectantly (none had diagnosis of ovarian cancer after at least 12 months of follow-up) and 63 patients (65 masses) underwent surgery and tumor removal (40 benign and 25 malignant tumors). Sensitivity and specificity for ultrasound, MRI, and ROMA were 96% and 93%, 100% and 81%, and 24% and 93%, respectively. The specificity of ultrasound was better than that for MRI (p=0.021), and the sensitivity of ultrasound was better than that for ROMA (p<0.001), sensitivity was better for MRI than for ROMA (p<0.001) and the specificity of ROMA was better than that for MRI (p<0.001). Ultrasound evaluation was the most effective and least costly method as compared with MRI and ROMA. CONCLUSION: In this study, ultrasound examination was the best second-step approach in inconclusive adnexal masses as determined by IOTA-SR, but the findings require confirmation in multicenter prospective trials.

A Controversial Old Topic Revisited: Should Diagnostic Hysteroscopy Be Routinely Performed Prior to the First IVF Cycle? A Systematic Review and Updated Meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aimed to analyze the impact of performing diagnostic hysteroscopy before the first in vitro fertilization (IVF) cycle on the clinical pregnancy rate and live birth. DATA SOURCES: PubMed-MEDLINE, Embase, Web of Science, The Cochrane Library, Gynecology and Fertility Specialized Register of Controlled Trials, and Google Scholar were consulted from inception to June 2022 using combinations of the relevant Medical Subject Headings terms and keywords. The search included major clinical trial registries such as ClinicalTrials.gov and the European EudraCT registry without language restrictions. In addition, manual cross-reference searches were also performed. METHODS OF STUDY SELECTION: All randomized and controlled clinical trials, prospective and retrospective cohort studies, and case-control studies comparing the probability of pregnancy and live birth among patients who underwent diagnostic hysteroscopy with possible treatment of any abnormal findings before the IVF cycle and patients who underwent the IVF cycle directly have been considered for inclusion. Studies with insufficient information on the results of interest or without the necessary information to perform the pooled analysis, those without a control group or with end points considered different than those of interest, were excluded. The review protocol was registered in PROSPERO (CRD42022354764). TABULATION, INTEGRATION, AND RESULTS: A total of 12 studies were included in the quantitative synthesis, reporting the reproductive outcomes of 5056 patients undergoing ART treatment for the first time. Selected studies included 6 randomized controlled trials, 1 prospective cohort study, 3 retrospective cohort studies, and 2 case-control studies. The likelihood of clinical pregnancy of patients undergoing hysteroscopy before IVF was significantly higher than those without hysteroscopy (odds ratio [OR], 1.49; 95% confidence CI 1.16-1.91; I2 = 69%). (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.22-1.88; I2 59%). Eight studies included live birth rate; no statistically significant differences were found between the 2 groups for this outcome (OR,1.24; 95% CI, 0.94-1.64; I2 = 62%). Subsequently, a sensitivity analysis was performed, including only randomized clinical trials. Clinical pregnancy OR of patients undergoing hysteroscopy before starting the IVF cycle remained significantly higher than the control group (OR,1.62, 95% CI, 1.15-2.29; I2 = 62%). Risk of bias assessment was performed using the Grading of Recommendations Assessment, Development, and Evaluation. CONCLUSION: The available scientific evidence suggests that performing routine hysteroscopy before the first IVF attempt improves the clinical pregnancy rate; however, the live birth rate is unaffected.

Preoperative Assessment of Cervical Involvement in Endometrial Cancer by Transvaginal Ultrasound and Magnetic Resonance Imaging: A Systematic Review and Meta-Analysis.

OBJECTIVE: To compare the diagnostic accuracy of transvaginal ultrasound (TVS) and magnetic resonance imaging (MRI) for detecting cervical infiltration by endometrial carcinoma using meta-analysis assessment. METHODS: An extensive search of papers comparing TVS and MRI for assessing cervical infiltration in endometrial cancer in the same set of patients was performed in Medline (Pubmed), Web of Science, and the Cochrane Database. Quality was assessed using QUADAS-2 tool (Quality Assessment of Diagnostic Accuracy Studies-2). Quantitative meta-analysis was performed. RESULTS: Our extended search identified 12 articles that used both techniques in the same set of patients and were included in the meta-analysis. The risk of bias for most studies was high for patient selection and index tests in QUADAS-2. Overall, the pooled estimated sensitivity and specificity for diagnosing cervical infiltration in women with endometrial cancer were identical for both techniques [69 % (95 % CI, 51 %-82 %) and 93 % (95 % CI, 90 %-95 %) for TVS, and 69 % (95 % CI, 57 %-79 %) and 91 % (95 % CI, 90 %-95 %) for MRI, respectively]. No statistical differences were found when comparing both methods. Heterogeneity was high for sensitivity and moderate for specificity when analyzing TVS and moderate for both sensitivity and specificity in the case of MRI. CONCLUSION: TVS and MRI showed very similar diagnostic performance for diagnosing cervical involvement in women with endometrial cancer.

Vaginal wall thickness as potential biomarker of vaginal health. A proposal for standardized ultrasound measurement using three-dimensional transvaginal ultrasound.

Vaginal wall thickness could be used as a biomarker of vaginal health. We propose a standardized method using three-dimensional (3D) ultrasound for measuring vaginal wall thickness. Fill the vagina with gel. Insert the endovaginal transducer into the vagina up to the middle third. In the sagittal plane, visualizing the cervix and vaginal fornices, capture a 3D volume of the upper third of the vagina. Using tomographic ultrasound imaging function in the sagittal plane and the posterior vaginal fornix as the reference obtain at least three axial planes of the vagina, separated by 1 cm. Measure the vaginal wall thickness at a distance of 2 cm from the posterior vaginal fornix at 12, 3, 6, and 9 o'clock. The reproducibility of measurements was high. Measurements of vaginal wall thickness can be reliably performed.

Transvaginal ultrasound versus magnetic resonance imaging for preoperative assessment of myometrial infiltration in patients with low-grade endometrioid endometrial cancer: A systematic review and head-to-head meta-analysis.

PURPOSE: We aimed to compare the diagnostic performance of magnetic resonance imaging (MRI) and transvaginal ultrasound (TVS) for detecting myometrial invasion (MI) in patients with low-grade endometrioid endometrial carcinoma. METHODS: A comprehensive search of MEDLINE (Pubmed), Web of Science, Embase and Scopus (from January 1990 to December 2022) was performed for articles comparing TVS and MRI in the evaluation of myometrial infiltration in low-grade (grade 1 or 2) endometrioid endometrial carcinoma in the same group of patients. We used QUADAS-2 tool for assessing the risk of bias of studies. RESULTS: We found 104 citations in our extensive research. Four articles were ultimately included in the meta-analysis, after excluding 100 reports. All articles were considered low risk of bias in most of the domains assessed in QUADAS-2. We observed that pooled sensitivity and specificity for detecting deep MI were 65% (95% confidence interval [CI] = 54%-75%) and 85% (95% CI = 79%-89%) for MRI, and 71% (95% CI = 63%-78%) and 76% (95% CI = 67%-83%) for TVS, respectively. No statistical differences were found between both imaging techniques (p > 0.05). We observed low heterogeneity for sensitivity and high for specificity regarding TVS; and moderate for both sensitivity and specificity in case of MRI. CONCLUSIONS: The diagnostic performance of TVS and MRI for the evaluation of deep MI in women with low-grade endometrioid endometrial cancer is similar. However, further research is needed as the number of studies is scanty.

The role of oncovascular surgery in gynecologic oncology surgery.

Oncovascular surgery is a new term used to define tumor resection with simultaneous reconstruction of the great vessels when the tumor infiltrates or firmly adheres to such vessels. The benefit of oncovascular surgery has been widely described in patients with hepato-biliary-pancreatic cancers, retroperitoneal soft tissue sarcoma, and in other areas of gynecologic oncology, such as the lateral compartment of the pelvis, retroperitoneum, and hepato-biliary-pancreatic region, with an increase in complete resections and without increasing the morbidity and mortality rates. In the latter decades of the past century, several advances and accumulating scientific evidence led gynecologic oncologists to perform more thorough cytoreductive surgeries that included multivisceral resections. But to our knowledge, published studies on the frequency and relevance of vascular surgery in gynecological oncology are scarce. Gynecologic oncologists still do not receive formal training in vascular surgery and additionally, with the current reduction in experience with pelvic and para-aortic lymphadenectomy, as well as other types of radical abdominal and pelvic surgeries, trainees will encounter fewer vascular injuries and the opportunity to deal with a variety of management types required. Well-organized collaboration between each subspecialty with a multidisciplinary approach and adequate pre-operative planning are pivotal. The aim of this review is to pave the way towards the understanding that patients with suspicion of great vessels' infiltration or encasement by tumor require personalized and specialized treatment with the need to form an oncovascular surgery team, and that it is necessary for gynecologic oncology surgeons to take a step forward in surgical training.

SUCCOR cone study: conization before radical hysterectomy.

OBJECTIVE: To evaluate disease-free survival of cervical conization prior to radical hysterectomy in patients with stage IB1 cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009). METHODS: A multicenter retrospective observational cohort study was conducted including patients from the Surgery in Cervical Cancer Comparing Different Surgical Aproaches in Stage IB1 Cervical Cancer (SUCCOR) database with FIGO 2009 IB1 cervical carcinoma treated with radical hysterectomy between January 1, 2013, and December 31, 2014. We used propensity score matching to minimize the potential allocation biases arising from the retrospective design. Patients who underwent conization but were similar for other measured characteristics were matched 1:1 to patients from the non-cone group using a caliper width ≤0.2 standard deviations of the logit odds of the estimated propensity score. RESULTS: We obtained a weighted cohort of 374 patients (187 patients with prior conization and 187 non-conization patients). We found a 65% reduction in the risk of relapse for patients who had cervical conization prior to radical hysterectomy (hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.16 to 0.75, p=0.007) and a 75% reduction in the risk of death for the same sample (HR 0.25, 95% CI 0.07 to 0.90, p=0.033). In addition, patients who underwent minimally invasive surgery without prior conization had a 5.63 times higher chance of relapse compared with those who had an open approach and previous conization (HR 5.63, 95% CI 1.64 to 19.3, p=0.006). Patients who underwent minimally invasive surgery with prior conization and those who underwent open surgery without prior conization showed no differences in relapse rates compared with those who underwent open surgery with prior cone biopsy (reference) (HR 1.94, 95% CI 0.49 to 7.76, p=0.349 and HR 2.94, 95% CI 0.80 to 10.86, p=0.106 respectively). CONCLUSIONS: In this retrospective study, patients undergoing cervical conization before radical hysterectomy had a significantly lower risk of relapse and death.

Recurrence Rate and Morbidity after Ultrasound-guided Transvaginal Aspiration of Ultrasound Benign-appearing Adnexal Cystic Masses with and without Sclerotherapy: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the pooled recurrence rate of benign adnexal masses/cysts (namely simple cyst, endometrioma, hydrosalpinx, peritoneal cyst) after transvaginal ultrasound-guided aspiration, with or without sclerotherapy. DATA SOURCES: Search of studies published in PubMed and Web of Science databases between January 1990 and December 2020. METHODS OF STUDY SELECTION: A systematic search strategy was done using Medical Subject Heading terms. Only randomized trials and prospective studies published in English language were included. TABULATION, INTEGRATION, AND RESULTS: A total of 395 articles were screened. After applying inclusion and exclusion criteria, 20 studies were included in this review comprising data from 1386 patients with a mean follow-up of 11.4 months (range 0.5-26.5 months). The overall pooled rate of recurrence of adnexal masses was 27%, (95% confidence interval [CI], 18%-39%). Recurrence rate was significantly higher after only aspiration than after sclerotherapy (53%; 95% CI, 46%-60% vs 14%; 95% CI, 8%-22%; p <.001). However, a high heterogeneity across the studies was found. A total of 10 major complications were recorded in the different publications. CONCLUSION: In a selected population, aspiration with sclerotherapy had a lower recurrence rate than aspiration without sclerotherapy. However, these results should be interpreted with caution given the heterogeneity of the studies and the paucity of randomized controlled trials. Regarding the adoption of this procedure in routine clinical practice, we believe that aspiration should be considered an experimental procedure as there are few studies addressing long-term recurrence rate, and data comparing this technique with surgical cystectomy are lacking.

Effect of Hysteroscopic Metroplasty on Reproductive Outcomes in Women with Septate Uterus: Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this systematic review with meta-analysis is to evaluate the impact of hysteroscopic metroplasty on adverse reproductive outcomes such as miscarriage, preterm birth, and fetal malpresentation in patients with history of infertility or previous poor obstetrical outcomes. DATA SOURCES: A systematic electronic search from inception each database up to April 2021 including the following databases was conducted: PubMed-MEDLINE, EMBASE, Web of Science, The Cochrane Library, the CGF Specialized Register of Controlled Trials, Google Scholar, and trial registries. A combination of the following keywords was used: uterine septum, septate uterus, congenital uterine malformation, class 2 uterus, class V uterus, metroplasty, hysteroscopic, pregnancy, clinical pregnancy, ongoing pregnancy, miscarriage, live birth, preterm birth, cesarean section, 'cesarean delivery, and fetal malpresentation. METHODS OF STUDY SELECTION: Studies comparing reproductive outcomes between women undergoing hysteroscopic resection of the uterine septum and those with expectant management were included. Eligible population consisted of infertile women, women with poor obstetrical history, or women without previous pregnancy failures and a diagnosis of septate uterus. TABULATION, INTEGRATION, AND RESULTS: The systematic electronic search retrieved 1076 studies; after elimination of duplicates, 688 titles and abstracts were screened, and 55 were assessed for eligibility. Eleven studies were included in the quantitative synthesis: one randomized controlled trial and 10 observational studies involving reproductive outcomes from 1589 patients with either complete or partial uterine septum. The pooled OR for miscarriage was 0.45, (95% CI, 0.22-0.90). When the analysis was performed considering subgroups according to the type of septum, pooled OR in complete septum subgroup was 0.16 (95% CI, 0.03-0.78), OR = 0.36 (95% CI, 0.19-0.71) in the partial septum subgroup and 0.58 (95% CI, 0.20-1.67) in those studies not differentiating between complete or partial septum. No significant differences were found between the 2 groups in OR of clinical pregnancy, term live birth, or risk of cesarean delivery. There was a significant decrease in the frequency of preterm birth in patients who underwent partial septum resection (OR = 0.30, 95% CI, 0.11-0.79). This difference was detected neither in patients with complete septum nor in studies not differentiating between partial or complete septum. The risk of fetal malpresentation was also significantly reduced (OR = 0.32, 95% CI, 0.16-0.65). CONCLUSION: The results of the present meta-analysis support that hysteroscopic metroplasty is effective in reducing the risk of miscarriage in patients with complete or partial uterine septum, although these data should be confirmed with a well-designed randomized controlled trial.

The Reproducibility of Ultrasonographic Findings of Rectosigmoid Endometriosis Among Examiners With Different Level of Expertise.

OBJECTIVE: To analyze the reproducibility of ultrasonographic (US) findings of rectosigmoid endometriosis among examiners with different level of expertise using stored three-dimensional (3D) volumes of the posterior compartment of the pelvis as a part of SANABA (Sardinia-Navarra-Barcelona) collaborative study. MATERIALS AND METHODS: Six examiners in 3 academic Department of Obstetrics and Gynecology, with different levels of experience and blinded to each other, evaluated 60 stored 3D volumes from the posterior compartment of the pelvis and looked for the presence or absence of features of rectosigmoid endometriotic lesions defined as an irregular hypoechoic nodule with or without hypoechoic foci at the level of the muscularis propria of the anterior wall rectum sigma. Multiplanar view and virtual navigation were used. All examiners had to assess the 3D volume of posterior compartment of the pelvis and classify it as present or absent disease. To analyze intra-observer and the inter-observer agreements, each examiner performed the assessment twice with a 2-week interval between the first and second assessments. Reproducibility was assessed by calculating the weighted Kappa index. RESULTS: Intra-observer reproducibility was moderate to very good for all observers (Kappa index ranging from 0.49 to 0.96) associated with a good diagnostic accuracy of each reader. Inter-observer reproducibility was fair to very good (Kappa index range: 0.21-0.87). CONCLUSIONS: The typical US sign of rectosigmoid endometriosis is reasonably recognizable to observers with different level of expertise when assessed in stored 3D volumes.

Two-Step Strategy for Optimizing the Preoperative Classification of Adnexal Masses in a University Hospital, Using International Ovarian Tumor Analysis Models: Simple Rules and Assessment of Different NEoplasias in the adneXa Model.

OBJECTIVES: To evaluate the performance of a two-step strategy compared with the International Ovarian Tumor Analysis (IOTA) - Assessment of Different NEoplasias in the adneXa (ADNEX) model for preoperative classification of adnexal masses. METHODS: An ambispective diagnostic accuracy study based on ultrasound data collected at one university hospital between 2012 and 2018. Two ultrasonographers classified the adnexal masses using IOTA Simple Rules (first step). Not classifiable masses were evaluated using the IOTA ADNEX model (second step). Also, all masses were classified using the IOTA ADNEX model. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-), and receiver operating characteristic (ROC) curve were estimated. A P value of <.05 was used to determine statistical significance. RESULTS: The study included 548 patients and 606 masses. Patients' median age was 41 years with an interquartile range between 32 and 51 years. In the first step, 89 (14%) masses were not classifiable. In the second step, 55 (61.8%) masses were classified as malignant. Furthermore, for the totality of 606 masses, the IOTA ADNEX model estimated the probability that 126 (20.8%) masses were malignant. The two-step strategy had a sensitivity, specificity, PPV, NPV, LR+, LR-, and ROC curve of 86.8%, 91.01%, 51.9%, 98.4%, 9.7, 0.1, and 0.889, respectively; compared to IOTA ADNEX model that had values of 91.8%, 87.16%, 44.4%, 99%, 7.1, 0.09, and 0.895, respectively. CONCLUSION: The two-step strategy shows a similar diagnostic performance when compared to the IOTA ADNEX model. The IOTA ADNEX model involves only one step and can be more practical, and thus would be recommended to use.

The Risk of Endometrial Malignancy and Other Endometrial Pathology in Women with Abnormal Uterine Bleeding: An Ultrasound-Based Model Development Study by the IETA Group.

OBJECTIVES: The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. DESIGN: The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. METHODS: A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model's ability to discriminate between the four outcomes and the calibration of risk estimates. RESULTS: The median age in 2,417 women was 50 (interquartile range 43-57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI: 0.85-0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. LIMITATIONS: Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable. CONCLUSIONS: The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate and locally recalibrate the model.

Myometrial wall thickness ratio-A nomogram reference for diagnosing myometrial wall asymmetry.

OBJECTIVE: Defining the normal range for the anterior/posterior myometrial wall thickness ratio in a cohort of women without adenomyosis or any other uterine wall anomaly on ultrasound examination. METHODS: Anterior and posterior miometrial wall thickness was measured in 555 women (mean age 34.6 years old, range: 20-50 years) without any ultrasound findings of adenomiosis or other uterine pathology. Measurements were performed in the longitudinal plane of a stored 3D volume. Two observers made all measurements. The myometrial wall thickness ratio was estimated and distribution by centiles obtained. Correlation of myometrial thickness ratio with patient's age and parity was also estimated, using the Pearson's correlation coefficient. Intra- and inter-observer reproducibility were estimated using the intra-class correlation coefficient (ICC). RESULTS: The mean ratio of the myometrial walls thickness (understood as anterior thickness/posterior thickness ratio) was 0.99 (95% CI: 0.96-1.01). The distribution of the ratio by centiles were as follows: 5%: 0.64, 10%: 0.70, 25%: 0.82, 50%: 0.96, 75%: 1.12, 90%: 1.30 and 95%: 1.45). The myometrial wall thickness ratio was not related to patient's age (Pearson's coefficient: 0.039, p = 0.371), neither to patient's parity (Pearson's coefficient: 0.004, p = 0.923). The ICC was 0.94 and 0.88 for observers 1 and 2, respectively. Inter-observer reproducibility was high (ICC: 0.83). CONCLUSIONS: Myometrial thickness ratio in women with normal uterus at ultrasound examination is about 1. However, centile distribution shows that values as low as 0.64 or as high as 1.45 could be considered as normal.

Severe pain during hysterosalpingo-contrast sonography (HyCoSy): a systematic review and meta-analysis.

PURPOSE: To assess the frequency of severe pain perception during hysterosalpingo-contrast sonography (HyCoSy) in infertile women and to assess whether there are differences in the frequency of associated pain according to the contrast used. DESIGN: Systematic review and meta-analysis. PATIENTS: Women undergoing HyCoSy due to infertility. INTERVENTIONS: Searches were carried out in two databases (Pubmed and Web of Science). We included prospective or retrospective cohort observational studies that specified the type of contrast used during HyCoSy and reported data regarding the number of patients who perceived severe pain during the procedure and the scale used for pain perception score. MAIN OUTCOME MEASURES: Pooled frequency of severe pain perception during HyCoSy and the pooled frequency of severe pain perception based on the contrast used. RESULTS: Twenty-nine studies were included in this meta-analysis including a total of 7139 patients. In 10 studies, Saline solution with air was used as contrast EchoVist™ was used in ten studies, in five studies, SonoVue™ was used and in four studies, ExEm-Foam™ was used as contrast. Pooled estimated frequency of severe pain perception during HyCoSy was 6% (95% CI 4-9). No statistically significant differences have been described regarding frequency of severe pain perception in relation to the different contrasts used. CONCLUSIONS: HyCoSy is a tolerable outpatient procedure. We did not find any evidence that one specific contrast was better tolerated than any other was.

SUCCOR study: an international European cohort observational study comparing minimally invasive surgery versus open abdominal radical hysterectomy in patients with stage IB1 cervical cancer.

BACKGROUND: Minimally invasive surgery in cervical cancer has demonstrated in recent publications worse outcomes than open surgery. The primary objective of the SUCCOR study, a European, multicenter, retrospective, observational cohort study was to evaluate disease-free survival in patients with stage IB1 (FIGO 2009) cervical cancer undergoing open vs minimally invasive radical hysterectomy. As a secondary objective, we aimed to investigate the association between protective surgical maneuvers and the risk of relapse. METHODS: We obtained data from 1272 patients that underwent a radical hysterectomy by open or minimally invasive surgery for stage IB1 cervical cancer (FIGO 2009) from January 2013 to December 2014. After applying all the inclusion-exclusion criteria, we used an inverse probability weighting to construct a weighted cohort of 693 patients to compare outcomes (minimally invasive surgery vs open). The first endpoint compared disease-free survival at 4.5 years in both groups. Secondary endpoints compared overall survival among groups and the impact of the use of a uterine manipulator and protective closure of the colpotomy over the tumor in the minimally invasive surgery group. RESULTS: Mean age was 48.3 years (range; 23-83) while the mean BMI was 25.7 kg/m2 (range; 15-49). The risk of recurrence for patients who underwent minimally invasive surgery was twice as high as that in the open surgery group (HR, 2.07; 95% CI, 1.35 to 3.15; P=0.001). Similarly, the risk of death was 2.42-times higher than in the open surgery group (HR, 2.45; 95% CI, 1.30 to 4.60, P=0.005). Patients that underwent minimally invasive surgery using a uterine manipulator had a 2.76-times higher hazard of relapse (HR, 2.76; 95% CI, 1.75 to 4.33; P<0.001) and those without the use of a uterine manipulator had similar disease-free-survival to the open surgery group (HR, 1.58; 95% CI, 0.79 to 3.15; P=0.20). Moreover, patients that underwent minimally invasive surgery with protective vaginal closure had similar rates of relapse to those who underwent open surgery (HR, 0.63; 95% CI, 0.15 to 2.59; P<0.52). CONCLUSIONS: Minimally invasive surgery in cervical cancer increased the risk of relapse and death compared with open surgery. In this study, avoiding the uterine manipulator and using maneuvers to avoid tumor spread at the time of colpotomy in minimally invasive surgery was associated with similar outcomes to open surgery. Further prospective studies are warranted.

Risk of complications in patients with conservatively managed ovarian tumours (IOTA5): a 2-year interim analysis of a multicentre, prospective, cohort study.

BACKGROUND: Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. METHODS: In the international, prospective, cohort International Ovarian Tumor Analysis Phase 5 (IOTA5) study, patients aged 18 years or older with at least one adnexal mass who had been selected for surgery or conservative management after ultrasound assessment were recruited consecutively from 36 cancer and non-cancer centres in 14 countries. Follow-up of patients managed conservatively is ongoing at present. In this 2-year interim analysis, we analysed patients who were selected for conservative management of an adnexal mass judged to be benign on ultrasound on the basis of subjective assessment of ultrasound images. Conservative management included ultrasound and clinical follow-up at intervals of 3 months and 6 months, and then every 12 months thereafter. The main outcomes of this 2-year interim analysis were cumulative incidence of spontaneous resolution of the mass, torsion or cyst rupture, or borderline or invasive malignancy confirmed surgically in patients with a newly diagnosed adnexal mass. IOTA5 is registered with ClinicalTrials.gov, number NCT01698632, and the central Ethics Committee and the Belgian Federal Agency for Medicines and Health Products, number S51375/B32220095331, and is ongoing. FINDINGS: Between Jan 1, 2012, and March 1, 2015, 8519 patients were recruited to IOTA5. 3144 (37%) patients selected for conservative management were eligible for inclusion in our analysis, of whom 221 (7%) had no follow-up data and 336 (11%) were operated on before a planned follow-up scan was done. Of 2587 (82%) patients with follow-up data, 668 (26%) had a mass that was already in follow-up at recruitment, and 1919 (74%) presented with a new mass at recruitment (ie, not already in follow-up in the centre before recruitment). Median follow-up of patients with new masses was 27 months (IQR 14-38). The cumulative incidence of spontaneous resolution within 2 years of follow-up among those with a new mass at recruitment (n=1919) was 20·2% (95% CI 18·4-22·1), and of finding invasive malignancy at surgery was 0·4% (95% CI 0·1-0·6), 0·3% (<0·1-0·5) for a borderline tumour, 0·4% (0·1-0·7) for torsion, and 0·2% (<0·1-0·4) for cyst rupture. INTERPRETATION: Our results suggest that the risk of malignancy and acute complications is low if adnexal masses with benign ultrasound morphology are managed conservatively, which could be of value when counselling patients, and supports conservative management of adnexal masses classified as benign by use of ultrasound. FUNDING: Research Foundation Flanders, KU Leuven, Swedish Research Council.