Ultrasonographic diagnosis of adnexal masses: interobserver agreement in the interpretation of videos, using IOTA terminology.

OBJECTIVES: Aim of this study is to estimate interobserver agreement in classifying adnexal tumors using IOTA terms, simple rules and subjective assessment. In addition, we related observers' accuracy with their experience in gynecological ultrasonography and the year of IOTA certification. METHODS: Eleven observers with three different levels of experience evaluated videoclips of 70 adnexal masses, defining tumor type according to IOTA terms and definitions, classifying the mass using IOTA Simple rules and Subjective assessment as well as providing Color Score evaluation. Sensitivity, specificity and area under the ROC curve were calculated and the year of IOTA certification was related with operators' accuracy through Pearson correlation coefficient. Interobserver agreement was estimated calculating percentage of agreement, Fleiss kappa and Cohen's kappa. RESULTS: We found a positive correlation between the year of IOTA certification and operators' accuracy (Pearson coefficient 0.694), especially among the observers with the least experience, the residents (p = 0.003). For tumor type classification, identification of papillary projections and classification of tumors using subjective assessment, agreement among all observers was moderate (Fleiss kappa 0.455, 0.552, and 0.476, respectively) and increased with the years of experience. Agreement in the application of Simple Rules was moderate in all examiners with IOTA certification, with Fleiss kappa in the range of (0.403, 0.498). For Color Score assignment interobserver agreement among all observers was fair (Cohen's kappa 0.380). CONCLUSIONS: Even among expert examiners, the results of adnexal lesion assessment can be inconsistent. Experience impacts on accuracy and agreement in subjective assessment, while the application of Simple Rules can mitigate the role of experience in interobserver agreement. The knowledge of IOTA models among residents seams to improve their diagnostic accuracy, showing the benefits of IOTA terminology for in training sonographers.

Prevalence and characteristics of thelarche variant.

Introduction: Girls with early thelarche may show an intermediate clinical picture between isolated premature thelarche (PT) and central precocious puberty (CPP), defined as "thelarche variant" (TV), characterized by an FSH-predominant response, although a univocal definition is lacking. Methods: Retrospective analysis on 91 girls with early thelarche (<8 years) and advanced bone age and/or accelerated growth who underwent 104 LHRH tests. Patients were classified into CPP (LH peak ≥5 IU/L; n = 28, 31%), TV (FSH peak ≥20 IU/L, LH peak <5 IU/L; n = 15, 16%), or PT (FSH peak <20 IU/L and LH peak <5 IU/L; n = 48, 53%). Results: TV patients were younger (5.51 years) and with less advanced bone age (+0.8 years). They had higher basal and peak FSH (2.5 and 26.6 IU/L) and lower basal and peak LH/FSH ratios (0.08 and 0.11). The prevalence of presence of ovarian follicles >5 mm in TV (42%) was similar to CPP but significantly higher than PT, whereas maximum ovarian volume was smaller in TV (1.0 cm3). At the last follow-up visit (available in 60% of the cases), 44% of TV developed CPP compared with 14% of PT (p = 0.04). At first evaluation, those who progressed to CPP had a higher basal FSH (3.2 IU/L), lower LH/FSH ratio (0.07), and a higher peak LH (4.1 IU/L) compared with those who did not progress to CPP (basal FSH 1.9 IU/L, p < 0.01; basal LH/FSH ratio 0.12, p < 0.01; peak LH 2.8 IU/L, p = 0.02). Conclusion: Using laboratory parameters only as a definition, we identified the clinical, laboratory, and imaging features of TV: these girls showed less advanced bone age and FSH predominance also at baseline, with smaller ovaries but with follicles >5 mm. Almost half of girls initially diagnosed as TV developed CPP at last follow-up visit, and these girls had higher baseline FSH, lower baseline LH/FSH ratio, and higher peak LH at first evaluation. Therefore, TV may represent a "precocious prepuberty" in which the FSH predominance may initially limit the progression into proper puberty, but it may eventually trigger full puberty (even CPP, depending on the girls' age).

Puzzling Out the Genetic Architecture of Endometriosis: Whole-Exome Sequencing and Novel Candidate Gene Identification in a Deeply Clinically Characterised Cohort.

Endometriosis (EM) is a common multifactorial gynaecological disorder. Although Genome-Wide Association Studies have largely been employed, the current knowledge of the genetic mechanisms underlying EM is far from complete, and other approaches are needed. To this purpose, whole-exome sequencing (WES) was performed on a deeply characterised cohort of 80 EM patients aimed at the identification of rare and damaging variants within 46 EM-associated genes and novel candidates. WES analysis detected 63 rare, predicted, and damaging heterozygous variants within 24 genes in 63% of the EM patients. In particular, (1) a total of 43% of patients carried variants within 13 recurrent genes (FCRL3, LAMA5, SYNE1, SYNE2, GREB1, MAP3K4, C3, MMP3, MMP9, TYK2, VEGFA, VEZT, RHOJ); (2) a total of 8.8% carried private variants within eight genes (KAZN, IL18, WT1, CYP19A1, IL1A, IL2RB, LILRB2, ZNF366); (3) a total of 24% carried variants within three novel candidates (ABCA13, NEB, CSMD1). Finally, to deepen the polygenic architecture of EM, a comprehensive evaluation of the analysed genes was performed, revealing a higher burden (p < 0.05) of genes harbouring rare and damaging variants in the EM patients than in the controls. These results highlight new insights into EM genetics, allowing for the definition of novel genotype-phenotype correlations, thereby contributing, in a long-term perspective, to the development of personalised care for EM patients.

External Validation of the Ovarian-Adnexal Reporting and Data System (O-RADS) Lexicon and the International Ovarian Tumor Analysis 2-Step Strategy to Stratify Ovarian Tumors Into O-RADS Risk Groups.

Importance: Correct diagnosis of ovarian cancer results in better prognosis. Adnexal lesions can be stratified into the Ovarian-Adnexal Reporting and Data System (O-RADS) risk of malignancy categories with either the O-RADS lexicon, proposed by the American College of Radiology, or the International Ovarian Tumor Analysis (IOTA) 2-step strategy. Objective: To investigate the diagnostic performance of the O-RADS lexicon and the IOTA 2-step strategy. Design, Setting, and Participants: Retrospective external diagnostic validation study based on interim data of IOTA5, a prospective international multicenter cohort study, in 36 oncology referral centers or other types of centers. A total of 8519 consecutive adult patients presenting with an adnexal mass between January 1, 2012, and March 1, 2015, and treated either with surgery or conservatively were included in this diagnostic study. Twenty-five patients were excluded for withdrawal of consent, 2777 were excluded from 19 centers that did not meet predefined data quality criteria, and 812 were excluded because they were already in follow-up at recruitment. The analysis included 4905 patients with a newly detected adnexal mass in 17 centers that met predefined data quality criteria. Data were analyzed from January 31 to March 1, 2022. Exposures: Stratification into O-RADS categories (malignancy risk <1%, 1% to <10%, 10% to <50%, and ≥50%). For the IOTA 2-step strategy, the stratification is based on the individual risk of malignancy calculated with the IOTA 2-step strategy. Main Outcomes and Measures: Observed prevalence of malignancy in each O-RADS risk category, as well as sensitivity and specificity. The reference standard was the status of the tumor at inclusion, determined by histology or clinical and ultrasonographic follow-up for 1 year. Multiple imputation was used for uncertain outcomes owing to inconclusive follow-up information. Results: Median age of the 4905 patients was 48 years (IQR, 36-62 years). Data on race and ethnicity were not collected. A total of 3441 tumors (70%) were benign, 978 (20%) were malignant, and 486 (10%) had uncertain classification. Using the O-RADS lexicon resulted in 1.1% (24 of 2196) observed prevalence of malignancy in O-RADS 2, 4% (34 of 857) in O-RADS 3, 27% (246 of 904) in O-RADS 4, and 78% (732 of 939) in O-RADS 5; the corresponding results for the IOTA 2-step strategy were 0.9% (18 of 1984), 4% (58 of 1304), 30% (206 of 690), and 82% (756 of 927). At the 10% risk threshold (O-RADS 4-5), the O-RADS lexicon had 92% sensitivity (95% CI, 87%-96%) and 80% specificity (95% CI, 74%-85%), and the IOTA 2-step strategy had 91% sensitivity (95% CI, 84%-95%) and 85% specificity (95% CI, 80%-88%). Conclusions and Relevance: The findings of this external diagnostic validation study suggest that both the O-RADS lexicon and the IOTA 2-step strategy can be used to stratify patients into risk groups. However, the observed malignancy rate in O-RADS 2 was not clearly below 1%.

Ultrasound-Guided Tru-Cut Biopsy in Gynecological and Non-Gynecological Pelvic Masses: A Single-Center Experience.

AIM: The aim of this study was to evaluate the feasibility of adequacy, accuracy, and safety of ultrasound-guided tru-cut biopsy in managing malignant and benign abdominopelvic masses in a selected population and critically discuss some issues in different situations, which deserve some reflections on those practices. MATERIALS AND METHODS: This is a retrospective study involving 42 patients who underwent transvaginal or transabdominal tru-cut biopsy between August 2017 and November 2021. The inclusion criteria were poor health status or primary inoperable advanced tumor, suspicion of recurrence or metastasis to the ovaries or peritoneum in gynecological and non-gynecological pelvic malignancies. Tissue samples were considered adequate if it was possible to determine the origin of the tumor, and immunohistochemistry could be performed. Diagnostic accuracy was assessed considering the agreement between tru-cut biopsy histology and final postoperative histology. RESULTS: It total, 44 biopsies were obtained from 42 patients (2 patients had repeat biopsies). The pathologist considered all pathological samples adequate (adequacy 100%). The final histology was consistent with tru-cut biopsy diagnosis in all but 2 cases (diagnostic accuracy 88.2%). If we consider only the cases that have carried out at least two diagnostic samples, accuracy rose to 94.1%. Pathological examinations from tru-cut samples showed 2 benign lesions (4.8%) and 40 malignant tumors (95.2%), divided into 19 advanced primary inoperable ovarian cancers, 7 primary advanced cervical cancers, 4 recurrent endometrial cancers, 3 recurrent cervical cancers, 3 recurrent ovarian cancers, 1 case of primitive peritoneal malignancy (leiomyosarcoma), and 3 non-gynecological cancers with a strong suspicion of metastases at ultrasound (2 cases of ovarian, colorectal cancer metastasis, and 1 case of pelvic site type B lymphoma metastasis). However, one case of minor complication related to the procedure was reported but not significant. CONCLUSIONS: The diagnostic adequacy, accuracy of the tru-cut biopsy, and safety were high. Pathological samples are representative of the disease and suitable for histological and immunohistochemical analysis.

Ultrasound Imaging of Acquired Myometrial Pseudoaneurysm: The Role of Manipulators as an Unusual Cause during Laparoscopic Surgery.

An acquired uterine artery myometrial pseudoaneurysm can occur due to inflammation, trauma, or iatrogenic causes, such as surgical procedures, and can lead to profuse bleeding. The efficacy of uterine manipulators in gynecological surgery, particularly as a cause of a pseudoaneurysm, has been poorly discussed in the literature. In this paper, we discuss a case of a 39-year-old woman with profuse uterine bleeding that occurred seven days after operative laparoscopic surgery for endometriosis. The color Doppler ultrasound better evoked the arterial-like turbulent blood flow inside this cavity. These sonographic features were highly suggestive of uterine artery pseudoaneurysm, presumably related to a secondary trauma caused by the manipulator. The diagnosis was subsequently re-confirmed by angiography, and the patient was treated conservatively with uterine artery embolization. Ultrasound has been shown to be a valuable and safe tool for imaging pseudoaneurysm and guiding subsequent interventional procedures. Accordingly, we briefly review the most suitable manipulators used in benign gynecological surgeries to verify if the different types in use can guide the surgeon towards the correct choice according to surgical needs and thus prevent potentially dangerous trauma.

Small extracellular vesicles from malignant ascites of patients with advanced ovarian cancer provide insights into the dynamics of the extracellular matrix.

The exact role of malignant ascites in the development of intraperitoneal metastases remains unclear, and the mechanisms by which extracellular vesicles (EVs) promote tumor progression in the pre-metastatic niche have not been fully discovered. In this study, we characterized ascites from high-grade epithelial ovarian cancer patients. Small-EVs (30-150 nm) were isolated from two sources-the bulk ascites and the ascitic fluid-derived tumor cell cultures-and assessed with a combination of imaging, proteomic profiling, and protein expression analyses. In addition, Gene Ontology and pathway analysis were performed using different databases and bioinformatic tools. The results proved that the small-EVs derived from the two sources exhibited significantly different stiffness and size distributions. The bulk ascitic fluid-derived small-EVs were predominantly involved in the complement and coagulation cascade. Small-EVs derived from ascites cell cultures contained a robust proteomic profile of extracellular matrix remodeling regulators, and we observed an increase in transforming growth factor-ß-I (TGFßI), plasminogen activator inhibitor 1 (PAI-1), and fibronectin expression after neoadjuvant chemotherapy. When measured in the two sources, we demonstrated that fibronectin exhibited opposite expression patterns in small-EVs in response to chemotherapy. These findings highlight the importance of an ascites cell isolation workflow in investigating the treatment-induced cancer adaption processes.

The Management of the Cotyledonoid Leiomyoma of the Uterus: A Narrative Review of the Literature.

Cotyledonoidleiomyoma is an unusual uterine myoma due to some ultrasound features that mimic a malignant lesion facilitating the choice of radical surgery. This study aims to summarize the ultrasound and the magnetic resonance imaging aspects of this atypical lesion, and also discuss surgical treatment and pathological exam. It included all English case reports or case series until August 2021 found through PubMed, Google Scholar, and Scopus. A total of 94 cotyledonoid leiomyomas were reported, with a median tumor size of 12 cm. The typical ultrasound image is characterized by a large solid heterogeneous mass, with high vascularity, no shadowing, and indistinct margins within the myometrium. Magnetic resonance imaging shows the presence of merging isointense nodules to the myometrium in T1-weighted images, hyperintense in T2-weighted images, and contrast agent enhancement. Surgical treatment consists of hysterectomy (75 cases, 80%) or myomectomy (19 cases, 20%), without evidence of recurrence if complete. The placenta-like appearance observed during surgery supports this rare fibroid hypothesis. The intraoperative frozen section can be considered. Microscopically, no atypical cells, signs of mitotic activity or cell necrosis are found. To conclude, some preoperative and intraoperative aspects of this lesion are distinctive and may lead surgeons to opt for conservative surgery.

"Nerve-sparing" laparoscopic treatment of parametrial ectopic pregnancy.

OBJECTIVE: To demonstrate laparoscopic surgical management of parametrial ectopic pregnancy. DESIGN: Video presentation of laparoscopic nerve-sparing treatment of parametrial pregnancy. SETTING: Tertiary university center. PATIENT(S): A 33-year-old patient, nullipara at 8 weeks of gestation, with no comorbidity and no previous surgery, was admitted to a spoke hospital for acute abdominal pain. During hospitalization, a transvaginal gynecologic ultrasound revealed pregnancy with ectopic localization. Free pelvic fluid was detected, and a subsequent diagnostic laparoscopy was performed because of worsening symptoms. During the procedure, hemoperitoneum drainage was instituted and American Society of Reproductive Medicine stage III pelvic endometriosis was diagnosed. A round formation approximately 3 cm in diameter was found at the left posterior parametrium (Fig. 1). Due to the pregnancy position and ß-human chorionic gonadotropic (ß-hCG; 820 mUI /mL) values, conservative treatment was chosen. Thus, methotrexate at 50 mg/m2 body surface area was administered. A second dose of methotrexate was administered seven days after the first one, and the ß-hCG increased to 1068 mUI. On day 14 after treatment, the ß-hCG was 1053 mUI/mL. Therefore, surgical treatment was chosen, and the patient was transferred to our center. An ultrasound assessment confirmed the ectopic pregnancy with a live fetus in the left posterior parametrium. INTERVENTION(S): The patient underwent operative laparoscopy to remove the ectopic pregnancy. Surgery was performed using a 3-dimensional optical system (TIPCAM 1, S D3-LINK; Karl Storz SE & Co., Tuttlingen, Germany). After drainage of the hemoperitoneum, the gestational sac was identified in the left posterior parametrium. The uterus, tubes, and ovaries showed normal morphology. Pelvic endometriosis was confirmed. After accessing the left pelvic retroperitoneum with the medial and lateral pararectal spaces' opening and development, ipsilateral ureterolysis was necessary to isolate the parametrial pregnancy in close contact with it. Coagulation and sectioning of the deep uterine veins were essential to control hemostasis. Identification of the left hypogastric nerve, which was partially infiltrated by the chorionic villi, and the pelvic splanchnic nerves, was required to safeguard them (Fig. 2). Subsequently, the surgeon decided to place a ureteral stent to prevent urologic complications. MAIN OUTCOME MEASURE(S): The laparoscopic approach proved to be safe and feasible to manage parametrial pregnancy. RESULT(S): The pregnancy was removed entirely. The patient was discharged 72 hours after the procedure with an uneventful postoperative course. The histologic report confirmed the diagnosis of parametrial pregnancy on decidualized endometriotic tissue. The ß-hCG serum level became negative in 20 days. CONCLUSION(S): Extrauterine pregnancies represent one of the leading causes of maternal death in the first trimester and constitute approximately 1%-2% of total pregnancies. Of these percentages, only 5%-8.3% are nontubal. Cases of abdominal pregnancy are even rarer, estimated at <1%, and among these, according to a recent review, only 20 cases of retroperitoneal pregnancy were described in the literature. The intraoperative finding of multiple endometriotic implants on the parietal peritoneum above the retroperitoneal pregnancy, together with the decidualized endometriosis result of the histologic examination have been considered to explain the pathogenesis of the condition. It is plausible to suppose that endometriosis has represented the access route for the fertilized ovum, which implanted on endometriotic superficial tissue and then moved toward the retroperitoneal vascularized structures. The diagnosis and treatment are challenging for the gynecologist. Medical treatment is a valid approach to uninterrupted early ectopic pregnancies; however, symptomatic patients' medical therapy failure is one indication for a surgical procedure. The laparoscopic method is optimal, especially in cases like the reported one, in which minimally-invasive techniques allowed complete removal of the pregnancy, respecting the anatomic structures of the retroperitoneum using nerve-sparing techniques. Furthermore, it ensured a safe ureteral stent placement without imaging. The laparoscopic surgical approach can be a safe and feasible option. It allows an early discharge, with a minimum risk of dysfunctional complications, and improves life quality compared to more destructive interventions. In conclusion, to control vascular, nervous, and urinary tract structures, surgical treatment should be based on anatomic knowledge of retroperitoneal anatomy to guarantee the best surgical outcome.

Cotyledonoid Leiomyoma Clinical Characteristics, Imaging Features, and Review of the Literature.

Cotyledonoid leiomyoma of the uterus is a rare variant of benign uterine leiomyoma. It has a favorable attitude, despite some ultrasound presentations. A bulky uterus with a heterogeneous mass with irregular margins, high vascularity, and infiltration of the myometrium can induce the suspicion of a malignant mesenchymal tumor and lead to a radical surgical treatment. If present, some imaging features may suggest this rare type of leiomyoma, thus avoiding extensive surgery, especially in young nulliparous women. We report 13 cases of cotyledonoid leiomyoma with clinical characteristics, imaging features, and a literature review.

Management of Non-Tubal Ectopic Pregnancies: A Single Center Experience.

Non-tubal ectopic pregnancies (NT-EPs) are rare but potentially life-threatening conditions. The incidence ranges are between 5-8.3% of all ectopic pregnancies. For this retrospective observational study, 16 patients with NT-EP and treated from January 2014 to May 2020 were recruited. Demographic details, symptoms, Beta human chorionic gonadotrophin (ß-hCG) levels, ultrasound findings, management and treatment outcomes were presented. In hemodynamically stable patients, diagnosis was made using ultrasounds and ß-hCG levels. Laparoscopy was essential to identify and remove the ectopic pregnancy in clinical unstable patients. A radical laparoscopic approach was chosen in one case of cervical pregnancy diagnosed late in the first trimester. Medical treatment and minimally invasive procedure, alone or combined, resulted in effective strategies in asymptomatic women with an early diagnosis of NT-EP. We report cases of cervical pregnancies successfully treated by hysteroscopy alone or combined with medical treatment, the first case of scar pregnancy treated by mini-reseptoscope and curettage and the fifth case of interstitial pregnancy treated with Methotrexate and Mifepristone. In this manuscript we report a single center experience in the management of NT-EPs with the aim of outlining the importance of the early diagnosis for a minimally invasive treatment in order to reduce maternal morbidity and mortality and preserve future fertility.

Conservative Treatment of Interstitial Ectopic Pregnancy with the Combination of Mifepristone and Methotrexate: Our Experience and Review of the Literature.

INTRODUCTION: Interstitial pregnancy (IP) is an ectopic pregnancy (EP) located in the portion of the fallopian tube that penetrates the uterine muscular layer. Incidence increased in the last two decades with the widespread use of the assisted reproductive techniques. It is estimated in 1-6% of all the EPs, with a maternal mortality rate of 2.0-2.5%. Clinical presentation, gestational age at diagnosis, beta-human chorionic gonadotropin (ß-hCG) levels, ultrasound features, and patient preference, should be considered to determine the best management: surgical, medical treatment, or close observation. We report two cases of IP successfully managed with systemic MTX and Mifepristone: in one case ß-hCG was >10.000 mIU/mL and a vital embryo was present. MATERIALS AND METHODS: A literature search was carried out on MEDLINE, EMBASE, and PUBMED. We identified two cases of IP referred to the Institute for Maternal and Child Burlo Garofolo, Trieste. Data related to clinical presentation, ß-hCG, and ultrasound scan at the moment of the diagnosis were recorded. In one of the cases, the ß-hCG level was >10.000 mIU/mL, and a vital embryo was testified at an ultrasound scan. The patient was asymptomatic and she was treated using multidose systemic Methotrexate (MTX) combined with Mifepristone. In the second case, in the presence of a clinically stable patient with ß - hCG > 10.000 mIU/mL, it was chosen that the administration of Mifepristone combined with a double dose of MTX. ß-hCG levels and ultrasound examinations were performed weekly until a complete resolution of the IP. RESULTS: In the first case, ß-hCG dropped down in 5 days and became undetachable in 30 days. In the second case, ß-hCG became undetectable in 47 days. The first-line therapy in asymptomatic women could be addressed to a combined protocol, consisting of a systemic multidose MTX regimen with a single oral dose of Mifepristone. CONCLUSIONS: Clinical management of IP remains a debated topic. In selected cases, a systemic multidose MTX regimen combined with a single oral dose of Mifepristone could be considered also in the presence of high serum ß-hCG.

Validation of models to diagnose ovarian cancer in patients managed surgically or conservatively: multicentre cohort study.

OBJECTIVE: To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. DESIGN: Multicentre cohort study. SETTING: 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. PARTICIPANTS: Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. MAIN OUTCOME MEASURES: Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. RESULTS: The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. CONCLUSIONS: Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. TRIAL REGISTRATION: ClinicalTrials.gov NCT01698632.

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.

Total Hysteroscopic Treatment of Cervical Pregnancy: The 2-step Technique.

STUDY OBJECTIVE: To evaluate the efficacy of total surgical treatment of ectopic cervical pregnancy [1] with a minimally invasive approach performed by hysteroscopy [2]. DESIGN: Step-by-step video demonstration of the surgical technique using 5 mm hysteroscopy followed by 10 mm resectoscopy. SETTING: A research and university hospital (IRCCS Burlo Garofolo, Trieste, Italy). PATIENTS: A 41-year-old woman with an ultrasound diagnosis of ectopic cervical pregnancy at 6 + 6 weeks of gestation with a beta human chorionic gonadotropin serum level of 55.951 mUI/mL. INTERVENTIONS: We performed a 2-step technique using 5- and 10-mm hysteroscopy (Video 1). During the first step, a 5-mm Bettocchi hysteroscope (Karl Storz, Tuttlingen, Germany) with a 5F bipolar electrode Versapoint Twizzle (Gynecare, Menlo Park, CA) was used. In this phase, the gestational sac was identified in order to confirm the diagnosis and its site of implantation. Later, the gestational sac was opened, and the pregnancy was terminated by cord section under an embryoscopic view (Fig. 1). Finally, a partial vessel coagulation was performed. Afterward, the cervix was dilated, and a resectoscopy was performed. During the second step, a 10-mm Gynecare resectoscope with the bipolar Gynecare Versapoint was used and the gestational sac with the embryo was removed; subsequently, a complete chorial villi resection was achieved. At last, a coagulation of bleeding vessels on the implantation site in order to control the hemostasis was performed (Fig. 2). MEASUREMENTS AND MAIN RESULTS: The study was approved by the institutional review board. The patient was discharged 24 hours after the procedure with an uneventful postoperative course, and the beta human chorionic gonadotropin serum level became negative in 20 days. After 40 days, the ultrasound cervical findings were regular, whereas office hysteroscopy showed the implantation site scar. After 5 months, the patient was pregnant with regular intrauterine implantation (Fig. 3). CONCLUSION: The total hysteroscopic approach with a 2-step technique offers an effective, safe, and minimally invasive surgical treatment to ectopic cervical pregnancy. Considering that our method, in contrast with the recent literature [3-5], is performed without any medical treatment, we reported for the first time an approach, that deserve more clinical data to confirm its effectiveness.

When Feeding Difficulties Are due to Genetics: The Case of Familial Partial 9q Duplication.

Chromosomal abnormalities may cause growth failure before or since birth. 9q duplication is reported as a cause of intrauterine growth restriction, mild dysmporphism, and intellectual disabilities. We report a case of a maternally inherited 9q21.31q21.33 duplication causing prenatal and postnatal growth restriction with feeding refusal and mild facial dysmorphisms, prenatally diagnosed by single-nucleotide polymorphism array analysis. Hypothesis of the possible pathogenic mechanisms are discussed.