Estimating risk of endometrial malignancy and other intracavitary uterine pathology in women without abnormal uterine bleeding using IETA-1 multinomial regression model: validation study.

OBJECTIVES: To assess the ability of the International Endometrial Tumor Analysis (IETA)-1 polynomial regression model to estimate the risk of endometrial cancer (EC) and other intracavitary uterine pathology in women without abnormal uterine bleeding. METHODS: This was a retrospective study, in which we validated the IETA-1 model on the IETA-3 study cohort (n = 1745). The IETA-3 study is a prospective observational multicenter study. It includes women without vaginal bleeding who underwent a standardized transvaginal ultrasound examination in one of seven ultrasound centers between January 2011 and December 2018. The ultrasonography was performed either as part of a routine gynecological examination, during follow-up of non-endometrial pathology, in the work-up before fertility treatment or before treatment for uterine prolapse or ovarian pathology. Ultrasonographic findings were described using IETA terminology and were compared with histology, or with results of clinical and ultrasound follow-up of at least 1 year if endometrial sampling was not performed. The IETA-1 model, which was created using data from patients with abnormal uterine bleeding, predicts four histological outcomes: (1) EC or endometrial intraepithelial neoplasia (EIN); (2) endometrial polyp or intracavitary myoma; (3) proliferative or secretory endometrium, endometritis, or endometrial hyperplasia without atypia; and (4) endometrial atrophy. The predictors in the model are age, body mass index and seven ultrasound variables (visibility of the endometrium, endometrial thickness, color score, cysts in the endometrium, non-uniform echogenicity of the endometrium, presence of a bright edge, presence of a single dominant vessel). We analyzed the discriminative ability of the model (area under the receiver-operating-characteristics curve (AUC); polytomous discrimination index (PDI)) and evaluated calibration of its risk estimates (observed/expected ratio). RESULTS: The median age of the women in the IETA-3 cohort was 51 (range, 20-85) years and 51% (887/1745) of the women were postmenopausal. Histology showed EC or EIN in 29 (2%) women, endometrial polyps or intracavitary myomas in 1094 (63%), proliferative or secretory endometrium, endometritis, or hyperplasia without atypia in 144 (8%) and endometrial atrophy in 265 (15%) women. The endometrial sample had insufficient material in five (0.3%) cases. In 208 (12%) women who did not undergo endometrial sampling but were followed up for at least 1 year without clinical or ultrasound signs of endometrial malignancy, the outcome was classified as benign. The IETA-1 model had an AUC of 0.81 (95% CI, 0.73-0.89, n = 1745) for discrimination between malignant (EC or EIN) and benign endometrium, and the observed/expected ratio for EC or EIN was 0.51 (95% CI, 0.32-0.82). The model was able to categorize the four histological outcomes with considerable accuracy: the PDI of the model was 0.68 (95% CI, 0.62-0.73) (n = 1532). The IETA-1 model discriminated very well between endometrial atrophy and all other intracavitary uterine conditions, with an AUC of 0.96 (95% CI, 0.95-0.98). Including only patients in whom the endometrium was measurable (n = 1689), the model's AUC was 0.83 (95% CI, 0.75-0.91), compared with 0.62 (95% CI, 0.52-0.73) when using endometrial thickness alone to predict malignancy (difference in AUC, 0.21; 95% CI, 0.08-0.32). In postmenopausal women with measurable endometrial thickness (n = 848), the IETA-1 model gave an AUC of 0.81 (95% CI, 0.71-0.91), while endometrial thickness alone gave an AUC of 0.70 (95% CI, 0.60-0.81) (difference in AUC, 0.11; 95% CI, 0.01-0.20). CONCLUSION: The IETA-1 model discriminates well between benign and malignant conditions in the uterine cavity in patients without abnormal bleeding, but it overestimates the risk of malignancy. It also discriminates well between the four histological outcome categories. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

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

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

Maternal hemodynamics and neonatal birth weight in pregnancies complicated by gestational diabetes: new insights from novel causal inference analysis modeling.

OBJECTIVE: Normal pregnancy is characterized by significant changes in maternal hemodynamics that are associated with fetal growth. Pregnancies complicated by gestational diabetes mellitus (GDM) are associated with large-for-gestational age and macrosomia, but the relationship between maternal hemodynamic parameters and birth weight (BW) among women with GDM has not been established. Our objective was to investigate the influence of maternal hemodynamics on neonatal BW in healthy pregnancies and in those complicated by GDM. METHODS: This was a prospective, cross-sectional case-control study of women aged ≥ 16 years with a singleton viable pregnancy, recruited between January 2016 and February 2021 at Leicester Royal Infirmary, Leicester, UK. GDM was defined as a fasting glucose level ≥ 5.3 mmol/L and/or serum glucose level ≥ 7.8 mmol/L, 2 h following a 75-g oral glucose load. We collected data on maternal characteristics and pregnancy outcome, including body mass index (BMI) at booking and BW centile adjusted for gestational age at delivery. Maternal hemodynamic parameters were assessed at 34-42 weeks' gestation using the Arteriograph® and bioreactance techniques. Graphical causal inference methodology was used to identify causal effects of the measured variables on neonatal BW centile. RESULTS: Included in the analysis were 141 women with GDM and 136 normotensive non-diabetic pregnant controls. 62% of the women with GDM were managed pharmacologically, with metformin and/or insulin. Variables included in the final model were cardiac output (CO), mean arterial pressure (MAP), total peripheral resistance (TPR), aortic augmentation index (AIx), aortic pulse wave velocity (PWV) and BMI at booking. Among the controls, maternal BMI, CO and aortic PWV were significantly associated with neonatal BW. Each SD increase in booking BMI produced an increase of 8.4 BW centiles (P = 0.002), in CO produced an increase of 9.4 BW centiles (P = 0.008) and in aortic PWV produced an increase of 7.1 BW centiles (P = 0.017). We found no significant relationship between MAP, TPR or aortic AIx and neonatal BW. Maternal hemodynamics influenced neonatal BW among the women with GDM in a similar manner to that in the control group, but only the relationship between maternal BMI and neonatal BW reached statistical significance, with a 1-SD increase in BMI producing an increase of 6.1 BW centiles (P = 0.019). CONCLUSIONS: Maternal BMI, CO and PWV were determinants of BW in our control group. The relationship between maternal hemodynamics and neonatal BW was similar between women with GDM and healthy controls. Our findings therefore suggest that fetal growth restriction in pregnancies complicated by GDM may indicate maternal cardiovascular dysfunction. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Ultrasound features of endometrial pathology in women without abnormal uterine bleeding: results from the International Endometrial Tumor Analysis study (IETA3).

OBJECTIVES: The primary aim of this study was to describe the ultrasound features of various endometrial and other intracavitary pathologies in women without abnormal uterine bleeding (AUB) using the International Endometrial Tumor Analysis (IETA) terminology. The secondary aim was to compare our findings with published data on women with AUB. METHODS: This was a prospective observational study of women presenting at one of seven centers specialized in gynecological ultrasonography, from 2011 until 2018, for indications unrelated to AUB. All patients underwent transvaginal ultrasound using the IETA examination and measurement techniques. Ultrasonography was performed as part of routine gynecological examination or follow-up of non-endometrial pathology, or as part of the work-up before undergoing treatment for infertility, uterine prolapse or ovarian pathology. Ultrasound findings were described using the IETA terminology. Endometrial sampling was performed after the ultrasound scan. The histological endpoints were endometrial atrophy, proliferative or secretory endometrium, endometrial hyperplasia without atypia, endometrial polyp, intracavitary leiomyoma, endometrial intraepithelial neoplasia (EIN), endometrial cancer (EC) and insufficient tissue. The findings in our cohort of women without AUB were compared with those in a published cohort of women with AUB who were examined with transvaginal ultrasound between 2012 and 2015 using the same IETA examination technique and terminology. RESULTS: In this study (IETA3), we included 1745 women without AUB who underwent a standardized transvaginal ultrasound examination followed by either endometrial sampling with histological diagnosis (n = 1537) or at least 1 year of clinical and ultrasound follow-up (n = 208). Of these, 858 (49.2%) women were premenopausal and 887 (50.8%) were postmenopausal. Histology showed the presence of EC and/or EIN in 29 (1.7%) women, endometrial polyps in 1028 (58.9%), intracavitary myomas in 66 (3.8%), proliferative or secretory changes or hyperplasia without atypia in 144 (8.3%), endometrial atrophy in 265 (15.2%) and insufficient tissue in five (0.3%). Most cases of EC or EIN (25/29 (86.2%)) were diagnosed after menopause. The mean endometrial thickness in women with EC or EIN was 11.2 mm (95% CI, 8.9-13.6 mm), being on average 2.4 mm (95% CI, 0.3-4.6 mm) thicker than their benign counterparts. Women with malignant endometrial pathology manifested more frequently non-uniform echogenicity (22/29 (75.9%)) than did those with benign endometrial pathology (929/1716 (54.1%)) (difference, +21.8% (95% CI, +4.2% to +39.2%)). Moderate to abundant vascularization (color score 3-4) was seen in 31.0% (9/29) of cases with EC or EIN compared with 12.8% (220/1716) of those with a benign outcome (difference, +18.2% (95% CI, -0.5% to +36.9%)). Multiple multifocal vessels were recorded in 24.1% (7/29) women with EC or EIN vs 4.0% (68/1716) of those with a benign outcome (difference, +20.2% (95% CI, +4.6% to +35.7%)). A regular endometrial-myometrial junction was seen less frequently in women with EC or EIN (19/29 (65.5%)) vs those with a benign outcome (1412/1716 (82.3%)) (difference, -16.8% (95% CI, -34.2% to +0.6%)). In women with endometrial polyps without AUB, a single dominant vessel was the most frequent vascular pattern (666/1028 (64.8%)). In women with EC, both in those with and those without AUB, the endometrium usually manifested heterogeneous echogenicity, but the endometrium was on average 8.6 mm (95% CI, 5.2-12.0 mm) thinner and less intensely vascularized (color score 3-4: difference, -26.8% (95% CI, -52.2% to -1.3%)) in women without compared to those with AUB. In both pre- and postmenopausal women, asymptomatic endometrial polyps were associated with a thinner endometrium, and they manifested more frequently a bright edge, a regular endometrial-myometrial junction and a single dominant vessel than did polyps in symptomatic women, and they were less intensely vascularized. CONCLUSIONS: We describe the typical ultrasound features of EC, polyps and other intracavitary histologies using IETA terminology in women without AUB. Our findings suggest that the presence of asymptomatic polyps or endometrial malignancy may be accompanied by thinner and less intensely vascularized endometria than their symptomatic counterparts. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

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

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

Imaging in gynecological disease (20): clinical and ultrasound characteristics of adnexal torsion.

OBJECTIVES: To describe the clinical and ultrasound characteristics of adnexal torsion. METHODS: This was a retrospective study. From the operative records of the eight participating gynecological ultrasound centers, we identified patients with a surgically confirmed diagnosis of adnexal torsion, defined as surgical evidence of ovarian pedicle, paraovarian cyst and/or Fallopian tube twisted on its own axis, who had undergone preoperative ultrasound examination by an experienced examiner, between 2008 and 2018. Only cases with at least two available ultrasound images and/or videoclips (one grayscale and one with Doppler evaluation) were included. Clinical, ultrasound, surgical and histological information was retrieved from each patient's medical record and entered into an Excel file by the principal investigator at each center. In addition, two authors reviewed all available ultrasound images and videoclips of the twisted adnexa, with regard to the presence of four predefined ultrasound features reported to be characteristic of adnexal torsion: (1) ovarian stromal edema with or without peripherally displaced antral follicles, (2) the follicular ring sign, (3) the whirlpool sign and (4) absence of vascularization in the twisted organ. RESULTS: A total of 315 cases of adnexal torsion were identified. The median age of the patients was 30 (range, 1-88) years. Most patients were premenopausal (284/314; 90.4%) and presented with acute or subacute pelvic pain (305/315; 96.8%). The surgical approach was laparoscopic in 239/312 (76.6%) patients and conservative surgery (untwisting with or without excision of a lesion) was performed in 149/315 (47.3%) cases. According to the original ultrasound reports, the median largest diameter of the twisted organ was 83 (range, 30-349) mm. Free fluid in the pouch of Douglas was detected in 196/275 (71.3%) patients. Ovarian stromal edema with or without peripherally displaced antral follicles was reported in the original ultrasound report in 167/241 (69.3%) patients, the whirlpool sign in 178/226 (78.8%) patients, absent color Doppler signals in the twisted organ in 119/269 (44.2%) patients and the follicular ring sign in 51/134 (38.1%) patients. On retrospective review of images and videoclips, ovarian stromal edema with or without peripherally displaced antral follicles (201/254; 79.1%) and the whirlpool sign (139/153; 90.8%) were the most commonly detected features of adnexal torsion. CONCLUSION: Most patients with surgically confirmed adnexal torsion are of reproductive age and present with acute or subacute pain. Common ultrasound signs are an enlarged adnexa, the whirlpool sign, ovarian stromal edema with or without peripherally displaced antral follicles and free fluid in the pelvis. The follicular ring sign and absence of Doppler signals in the twisted organ are slightly less common signs. Recognizing ultrasound signs of adnexal torsion is important so that the correct treatment, i.e. surgery without delay, can be offered. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Predicting locally advanced rectal cancer response to neoadjuvant therapy with 18F-FDG PET and MRI radiomics features.

PURPOSE: Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15-30% of cases, therefore it would be useful to assess if pretreatment of 18F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC. METHODS: Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models. RESULTS: In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index). CONCLUSIONS: If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.

Imaging in gynecological disease (16): clinical and ultrasound characteristics of serous cystadenofibromas in adnexa.

OBJECTIVE: To describe the clinical and ultrasound characteristics of serous cystadenofibromas in the adnexa. METHODS: This was a retrospective study of patients identified in the International Ovarian Tumor Analysis (IOTA) database, who had a histological diagnosis of serous cystadenofibroma and had undergone preoperative ultrasound examination by an experienced ultrasound examiner, between 1999 and 2012. In the IOTA database, which contains data collected prospectively, the tumors were described using the terms and definitions of the IOTA group. In addition, three authors reviewed, first independently and then together, ultrasound images of serous cystadenofibromas and described them using pattern recognition. RESULTS: We identified 233 women with a histological diagnosis of serous cystadenofibroma. In the IOTA database, most cystadenofibromas (67.4%; 157/233) were described as containing solid components but 19.3% (45/233) were described as multilocular cysts and 13.3% (31/233) as unilocular cysts. Papillary projections were described in 52.4% (122/233) of the cystadenofibromas. In 79.5% (97/122) of the cysts with papillary projections, color Doppler signals were absent in the papillary projections. Most cystadenofibromas (83.7%; 195/233) manifested no or minimal color Doppler signals. On retrospective analysis of 201 ultrasound images of serous cystadenofibromas, using pattern recognition, 10 major types of ultrasound appearance were identified. The most common pattern was a unilocular solid cyst with one or more papillary projections, but no other solid components (25.9%; 52/201). The second most common pattern was a multilocular solid mass with small solid component(s), but no papillary projections (19.4%; 39/201). The third and fourth most common patterns were multi- or bilocular cyst (16.9%; 34/201) and unilocular cyst (11.9%; 24/201). Using pattern recognition, shadowing was identified in 39.8% (80/201) of the tumors, and microcystic appearance of the papillary projections was observed in 34 (38.6%) of the 88 tumors containing papillary projections. CONCLUSIONS: The ultrasound features of serous cystadenofibromas vary. The most common pattern is a unilocular solid cyst with one or more papillary projections but no other solid components, with absent color Doppler signals. Most serous cystadenofibromas were poorly vascularized on color Doppler examination and many manifested acoustic shadowing. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma.

BACKGROUND: Effective target therapies for intrahepatic cholangiocarcinoma (ICC) have not been identified so far. One of the reasons may be the genetic evolution from primary (PR) to recurrent (REC) tumors. We aim to identify peculiar characteristics and to select potential targets specific for recurrent tumors. Eighteen ICC paired PR and REC tumors were collected from 5 Italian Centers. Eleven pairs were analyzed for gene expression profiling and 16 for mutational status of IDH1. For one pair, deep mutational analysis by Next Generation Sequencing was also carried out. An independent cohort of patients was used for validation. RESULTS: Two class-paired comparison yielded 315 differentially expressed genes between REC and PR tumors. Up-regulated genes in RECs are involved in RNA/DNA processing, cell cycle, epithelial to mesenchymal transition (EMT), resistance to apoptosis, and cytoskeleton remodeling. Down-regulated genes participate to epithelial cell differentiation, proteolysis, apoptotic, immune response, and inflammatory processes. A 24 gene signature is able to discriminate RECs from PRs in an independent cohort; FANCG is statistically associated with survival in the chol-TCGA dataset. IDH1 was mutated in the RECs of five patients; 4 of them displayed the mutation only in RECs. Deep sequencing performed in one patient confirmed the IDH1 mutation in REC. CONCLUSIONS: RECs are enriched for genes involved in EMT, resistance to apoptosis, and cytoskeleton remodeling. Key players of these pathways might be considered druggable targets in RECs. IDH1 is mutated in 30% of RECs, becoming both a marker of progression and a target for therapy.

Ultrasound characteristics of endometrial cancer as defined by International Endometrial Tumor Analysis (IETA) consensus nomenclature: prospective multicenter study.

OBJECTIVE: To describe the sonographic features of endometrial cancer in relation to tumor stage, grade and histological type, using the International Endometrial Tumor Analysis (IETA) terminology. METHODS: This was a prospective multicenter study of 1714 women with biopsy-confirmed endometrial cancer undergoing standardized transvaginal grayscale and Doppler ultrasound examination according to the IETA study protocol, by experienced ultrasound examiners using high-end ultrasound equipment. Clinical and sonographic data were entered into a web-based database. We assessed how strongly sonographic characteristics, according to IETA, were associated with outcome at hysterectomy, i.e. tumor stage, grade and histological type, using univariable logistic regression and the c-statistic. RESULTS: In total, 1538 women were included in the final analysis. Median age was 65 (range, 27-98) years, median body mass index was 28.4 (range 16-67) kg/m2 , 1377 (89.5%) women were postmenopausal and 1296 (84.3%) reported abnormal vaginal bleeding. Grayscale and color Doppler features varied according to grade and stage of tumor. High-risk tumors, compared with low-risk tumors, were less likely to have regular endometrial-myometrial junction (difference of -23%; 95% CI, -27 to -18%), were larger (mean endometrial thickness; difference of +9%; 95% CI, +8 to +11%), and were more likely to have non-uniform echogenicity (difference of +7%; 95% CI, +1 to +13%), a multiple, multifocal vessel pattern (difference of +21%; 95% CI, +16 to +26%) and a moderate or high color score (difference of +22%; 95% CI, +18 to +27%). CONCLUSION: Grayscale and color Doppler sonographic features are associated with grade and stage of tumor, and differ between high- and low-risk endometrial cancer. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells.

PURPOSE: Recent evidences indicates that hydroxytyrosol, one of the main olive oil phenols, possess antitumor effects because of its pro-oxidant properties and the capacity to inhibit proliferation and to promote apoptosis in several tumor cell lines, although most of the results were obtained for breast and digestive systems cancers. METHODS: In this study, we evaluated the activities of hydroxytyrosol against papillary (TPC-1, FB-2) and follicular (WRO) thyroid cancer cell lines. RESULTS: Cellular viability revealed that high doses of hydroxytyrosol reduced cancer cells viability concomitantly with a reduction of cyclin D1 expression and an up-regulation of cell cycle key modulator p21 levels. In the same experimental conditions, Annexin V-PI staining and DNA laddering revealed that hydroxytyrosol exerts proapoptotic effects on papillary and follicular cancer cells. Furthermore, by Western blot analysis, we observed that hydroxytyrosol treatment reduced thyroid cancer cells viability by promoting apoptotic cell death via intrinsic pathway. CONCLUSIONS: Collectively, our results demonstrated for the first time that in thyroid cancer cells hydroxytyrosol promoted apoptosis at higher doses with respect to other cancer cells lines. Therefore, further studies will reveal the mechanisms by which thyroid cancer cells are more resistant to the proapoptotic effect exerted by hydroxytyrosol as well as the potential application as novel target therapeutic in thyroid cancer.

Lenalidomide normalizes tumor vessels in colorectal cancer improving chemotherapy activity.

BACKGROUND: Angiogenesis inhibition is a promising approach for treating metastatic colorectal cancer (mCRC). Recent evidences support the seemingly counterintuitive ability of certain antiangiogenic drugs to promote normalization of residual tumor vessels with important clinical implications. Lenalidomide is an oral drug with immune-modulatory and anti-angiogenic activity against selected hematologic malignancies but as yet little is known regarding its effectiveness for solid tumors. The aim of this study was to determine whether lenalidomide can normalize colorectal cancer neo-vessels in vivo, thus reducing tumor hypoxia and improving the benefit of chemotherapy. METHODS: We set up a tumorgraft model with NOD/SCID mice implanted with a patient-derived colorectal cancer liver metastasis. The mice were treated with oral lenalidomide (50 mg/Kg/day for 28 days), intraperitoneal 5-fluorouracil (5FU) (20 mg/Kg twice weekly for 3 weeks), combination (combo) of lenalidomide and 5FU or irrelevant vehicle. We assessed tumor vessel density (CD146), pericyte coverage (NG2; alphaSMA), in vivo perfusion capability of residual vessels (lectin distribution essay), hypoxic areas (HP2-100 Hypoxyprobe) and antitumor activity in vivo and in vitro. RESULTS: Treatment with lenalidomide reduced tumor vessel density (p = 0.0001) and enhanced mature pericyte coverage of residual vessels (p = 0.002). Perfusion capability of tumor vessels was enhanced in mice treated with lenalidomide compared to controls (p = 0.004). Accordingly, lenalidomide reduced hypoxic tumor areas (p = 0.002) and enhanced the antitumor activity of 5FU in vivo. The combo treatment delayed tumor growth (p = 0.01) and significantly reduced the Ki67 index (p = 0.0002). Lenalidomide alone did not demonstrate antitumor activity compared to untreated controls in vivo or against 4 different mCRC cell lines in vitro. CONCLUSIONS: We provide the first evidence of tumor vessel normalization and hypoxia reduction induced by lenalidomide in mCRC in vivo. This effect, seemingly counterintuitive for an antiangiogenic compound, translates into indirect antitumor activity thus enhancing the therapeutic index of chemotherapy. Our findings suggest that further research should be carried out on synergism between lenalidomide and conventional therapies for treating solid tumors that might benefit from tumor vasculature normalization.

Early cytomegalovirus-specific T-cell response and estimated glomerular filtration rate identify patients at high risk of infection after renal transplantation.

BACKGROUND: Assessing the risk of cytomegalovirus (CMV) viremia in kidney transplant recipients (KTR) may be helpful to indicate in which patient it is worth starting antiviral treatment during preemptive strategy. METHODS: In 40 CMV-seropositive KTR preemptively treated with ganciclovir, we used interferon (IFN)-γ ELISpot test to evaluate whether monitoring T cells directed against phosphoprotein (pp) 65 and immediate early (IE)-1 antigens could predict the onset of viremia. RESULTS: CMV viremia occurred in 24 patients (60%) within 120 days after transplantation. Non-viremic patients had higher anti-pp65, anti-IE-1 T cells, and estimated glomerular filtration rate (eGFR) in the first 90 days after transplantation. At logistic regression, anti-pp65, anti-IE-1 T cells, and eGFR measured at day 30 were significantly associated with CMV infection. Cutoff values of 15 spot-forming cells (SFCs)/200,000 peripheral blood mononuclear cells (PBMCs) for anti-IE, 40 SFCs/200,000 PBMCs for anti-pp65, and 46.6 mL/min/1.73 m(2) for eGFR, respectively, predicted the risk of CMV infection with high sensitivity and specificity (area under the receiver operating characteristic curve >0.75). Using a classification tree model, we identified as high-risk patients those showing anti-pp65 <42 SFCs/200,000 PBMCs and eGFR <62 mL/min/1.73 m(2) , as well as anti-pp65 ≥42 and anti-IE-1 <6.5 SFCs/200,000 PBMCs. CONCLUSION: Monitoring CMV-specific T-cell responses and eGFR in the first month post transplant can identify patients at high risk of CMV infection, for whom preemptive antiviral therapy is recommended.

Systematic approach to sonographic evaluation of the pelvis in women with suspected endometriosis, including terms, definitions and measurements: a consensus opinion from the International Deep Endometriosis Analysis (IDEA) group.

The IDEA (International Deep Endometriosis Analysis group) statement is a consensus opinion on terms, definitions and measurements that may be used to describe the sonographic features of the different phenotypes of endometriosis. Currently, it is difficult to compare results between published studies because authors use different terms when describing the same structures and anatomical locations. We hope that the terms and definitions suggested herein will be adopted in centers around the world. This would result in consistent use of nomenclature when describing the ultrasound location and extent of endometriosis. We believe that the standardization of terminology will allow meaningful comparisons between future studies in women with an ultrasound diagnosis of endometriosis and should facilitate multicenter research. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Hourly interaction between wind speed and energy fluxes in Brazilian Wetlands - Mato Grosso - Brazil.

Matter and energy flux dynamics of wetlands are important to understand environmental processes that govern biosphere-atmosphere interactions across ecosystems. This study presents analyses about hourly interaction between wind speed and energy fluxes in Brazilian Wetlands - Mato Grosso - Brazil. This study was conducted in Private Reserve of Natural Heritage (PRNH SESC, 16º39'50''S; 56º47'50''W) in Brazilian Wetland. According to Curado et al. (2012), the wet season occurs between the months of January and April, while the June to September time period is the dry season. Results presented same patterns in energies fluxes in all period studied. Wind speed and air temperature presented same patterns, while LE was relative humidity presented inverse patterns of the air temperature. LE was predominant in all seasons and the sum of LE and H was above 90% of net radiation. Analyses of linear regression presented positive interactions between wind speed and LE, and wind speed and H in all seasons, except in dry season of 2010. Confidence coefficient regression analyses present statistical significance in all wet and dry seasons, except dry season of 2010, suggest that LE and H had interaction with other micrometeorological variables.

Modeling the reflection of Photosynthetically active radiation in a monodominant floodable forest in the Pantanal of Mato Grosso State using multivariate statistics and neural networks.

The study of radiation entrance and exit dynamics and energy consumption in a system is important for understanding the environmental processes that rule the biosphere-atmosphere interactions of all ecosystems. This study provides an analysis of the interaction of energy in the form of photosynthetically active radiation (PAR) in the Pantanal, a Brazilian wetland forest, by studying the variation of PAR reflectance and its interaction with local rainfall. The study site is located in Private Reserve of Natural Heritage, Mato Grosso State, Brazil, where the vegetation is a monodominant forest of Vochysia divergens Phol. The results showed a high correlation between the reflection of visible radiation and rainfall; however, the behavior was not the same at the three heights studied. An analysis of the hourly variation of the reflected waves also showed the seasonality of these phenomena in relation to the dry and rainy seasons. A predictive model for PAR was developed with a neural network that has a hidden layer, and it showed a determination coefficient of 0.938. This model showed that the Julian day and time of measurements had an inverse association with the wind profile and a direct association with the relative humidity profile.

Vegan-vegetarian diets in pregnancy: danger or panacea? A systematic narrative review.

BACKGROUND: Although vegan-vegetarian diets are increasingly popular, no recent systematic reviews on vegan-vegetarian diets in pregnancy exist. OBJECTIVES: To review the literature on vegan-vegetarian diets and pregnancy outcomes. SEARCH STRATEGY: PubMed, Embase, and the Cochrane library were searched from inception to September 2013 for pregnancy and vegan or vegetarian Medical Subject Headings (MeSH) and free-text terms. SELECTION CRITERIA: Vegan or vegetarian diets in healthy pregnant women. We excluded case reports and papers analysing vegan-vegetarian diets in poverty and malnutrition. Searching, paper selection, and data extraction were performed in duplicate. DATA COLLECTION AND ANALYSIS: The high heterogeneity of the studies led to a narrative review. MAIN RESULTS: We obtained 262 full texts from 2329 references; 22 selected papers reporting maternal-fetal outcomes (13) and dietary deficiencies (nine) met the inclusion criteria. None of the studies reported an increase in severe adverse outcomes or in major malformations, except one report of increased hypospadias in infants of vegetarian mothers. Five studies reported vegetarian mothers had lower birthweight babies, yet two studies reported higher birthweights. The duration of pregnancy was available in six studies and was similar between vegan-vegetarians and omnivores. The nine heterogeneous studies on microelements and vitamins suggest vegan-vegetarian women may be at risk of vitamin B12 and iron deficiencies. AUTHOR'S CONCLUSIONS: The evidence on vegan-vegetarian diets in pregnancy is heterogeneous and scant. The lack of randomised studies prevents us from distinguishing the effects of diet from confounding factors. Within these limits, vegan-vegetarian diets may be considered safe in pregnancy, provided that attention is paid to vitamin and trace element requirements.

Transvaginal ultrasound assessment of myometrial and cervical stromal invasion in women with endometrial cancer: interobserver reproducibility among ultrasound experts and gynecologists.

OBJECTIVES: To assess interobserver reproducibility among ultrasound experts and gynecologists in the prediction by transvaginal ultrasound of deep myometrial and cervical stromal invasion in women with endometrial cancer. METHODS: Sonographic videoclips of the uterine corpus and cervix of 53 women with endometrial cancer, examined preoperatively by the same ultrasound expert, were integrated into a digitalized survey. Nine ultrasound experts and nine gynecologists evaluated presence or absence of deep myometrial and cervical stromal invasion. Histopathology from hysterectomy specimens was used as the gold standard. RESULTS: Compared with gynecologists, ultrasound experts showed higher sensitivity, specificity and agreement with histopathology in the assessment of cervical stromal invasion (42% (95% CI, 31-53%) vs 57% (95% CI, 45-68%), P < 0.01; 83% (95% CI, 78-86%) vs 87% (95% CI, 83-90%), P = 0.02; and kappa, 0.45 (95% CI, 0.40-0.49) vs 0.58 (95% CI, 0.53-0.62), P < 0.001, respectively) but not of deep myometrial invasion (73% (95% CI, 66-79%) vs 73% (95% CI, 66-79%), P = 1.0; 70% (95% CI, 65-75%) vs 69% (95% CI, 63-74%), P = 0.68; and kappa, 0.48 (95% CI, 0.44-0.53) vs 0.52 (95% CI, 0.48-0.57), P = 0.11, respectively). Though interobserver reproducibility (in the context of test proportions 'good' and 'very good', according to kappa) regarding deep myometrial invasion did not differ between the groups (experts, 34% vs gynecologists, 22%, P = 0.13), ultrasound experts assessed cervical stromal invasion with significantly greater interobserver reproducibility than did gynecologists (53% vs 14%, P < 0.001). CONCLUSION: Preoperative ultrasound assessment of deep myometrial and cervical stromal invasion in endometrial cancer is best performed by ultrasound experts, as, compared with gynecologists, they showed a greater degree of agreement with histopathology and greater interobserver reproducibility in the assessment of cervical stromal invasion.

Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group.

The MUSA (Morphological Uterus Sonographic Assessment) statement is a consensus statement on terms, definitions and measurements that may be used to describe and report the sonographic features of the myometrium using gray-scale sonography, color/power Doppler and three-dimensional ultrasound imaging. The terms and definitions described may form the basis for prospective studies to predict the risk of different myometrial pathologies, based on their ultrasound appearance, and thus should be relevant for the clinician in daily practice and for clinical research. The sonographic features and use of terminology for describing the two most common myometrial lesions (fibroids and adenomyosis) and uterine smooth muscle tumors are presented.