| 1. |
- Thompson, B.A., et al.
(author)
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Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
- 2014
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
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Journal article (peer-reviewed)abstract
- The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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| 2. |
- Ameye, L., et al.
(author)
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Clinically oriented three-step strategy for assessment of adnexal pathology
- 2012
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:5, s. 582-591
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Journal article (peer-reviewed)abstract
- Objective To determine the diagnostic performance of ultrasound-based simple rules, risk of malignancy index (RMI), two logistic regression models (LR1 and LR2) and real-time subjective assessment by experienced ultrasound examiners following the exclusion of masses likely to be judged as easy and 'instant' to diagnose by an ultrasound examiner, and to develop a new strategy for the assessment of adnexal pathology based on this. Methods 3511 patients with at least one persistent adnexal mass preoperatively underwent transvaginal ultrasonography to assess tumor morphology and vascularity. They were included in two consecutive prospective studies by the International Ovarian Tumor Analysis (IOTA) group: Phase 1 (1999-2005), development of the simple rules and logistic regression models LR1 and LR2, and Phase 2, a validation study (2005-2007). Results Almost half of the cases (43%) were identified as 'instant' to diagnose on the basis of descriptors applied to the database. To assess diagnostic performance in the more difficult 'non-instant' masses, we used only Phase 2 data (n = 1036). The sensitivity of LR2 was 88%, of RMI it was 41% and of subjective assessment it was 87%. The specificity of LR2 was 67%, of RMI it was 90% and of subjective assessment it was 86%. The simple rules yielded a conclusive result in almost 2/3 of the masses, where they resulted in sensitivity and specificity similar to those of real-time subjective assessment by experienced ultrasound examiners: sensitivity 89 vs 89% (P = 0.76), specificity 91 vs 91% (P = 0.65). When a three-step strategy was appliedwith easy 'instant' diagnoses as Step 1, simple rules where conclusive as Step 2 and subjective assessment by an experienced ultrasound examiner in the remaining masses as Step 3, we obtained a sensitivity of 92% and specificity of 92% compared with sensitivity 90% (P = 0.03) and specificity 93% (P = 0.44) when using real-time subjective assessment by experts in all tumors. Conclusion A diagnostic strategy using simple descriptors and ultrasound rules when applied to the variables contained in the IOTA database obtains results that are at least as good as those obtained by subjective assessment of a mass by an expert. Copyright. (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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| 3. |
- Di Legge, A., et al.
(author)
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Lesion size affects diagnostic performance of IOTA logistic regression models, IOTA simple rules and risk of malignancy index in discriminating between benign and malignant adnexal masses
- 2012
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 40:3, s. 345-354
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Journal article (peer-reviewed)abstract
- Objectives To estimate the ability to discriminate between benign and malignant adnexal masses of different size using: subjective assessment, two International Ovarian Tumor Analysis (IOTA) logistic regression models (LR1 and LR2), the IOTA simple rules and the risk of malignancy index (RMI). Methods We used a multicenter IOTA database of 2445 patients with at least one adnexal mass, i.e. the database previously used to prospectively validate the diagnostic performance of LR1 and LR2. The masses were categorized into three subgroups according to their largest diameter: small tumors (diameter < 4 cm; n = 396), medium-sized tumors (diameter, 49.9 cm; n = 1457) and large tumors (diameter = 10 cm, n = 592). Subjective assessment, LR1 and LR2, IOTA simple rules and the RMI were applied to each of the three groups. Sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-), diagnostic odds ratio (DOR) and area under the receiveroperating characteristics curve (AUC) were used to describe diagnostic performance. A moving window technique was applied to estimate the effect of tumor size as a continuous variable on the AUC. The reference standard was the histological diagnosis of the surgically removed adnexal mass. Results The frequency of invasive malignancy was 10% in small tumors, 19% in medium-sized tumors and 40% in large tumors; 11% of the large tumors were borderline tumors vs 3% and 4%, respectively, of the small and medium-sized tumors. The type of benign histology also differed among the three subgroups. For all methods, sensitivity with regard to malignancy was lowest in small tumors (5684% vs 6793% in medium-sized tumors and 7495% in large tumors) while specificity was lowest in large tumors (6087%vs 8395% in medium-sized tumors and 8396% in small tumors ). The DOR and the AUC value were highest in medium-sized tumors and the AUC was largest in tumors with a largest diameter of 711 cm. Conclusion Tumor size affects the performance of subjective assessment, LR1 and LR2, the IOTA simple rules and the RMI in discriminating correctly between benign and malignant adnexal masses. The likely explanation, at least in part, is the difference in histology among tumors of different size. Copyright (C) 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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| 4. |
- Mascilini, F., et al.
(author)
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Imaging in gynecological disease (10): clinical and ultrasound characteristics of decidualized endometriomas surgically removed during pregnancy
- 2014
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 44:3, s. 354-360
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Journal article (peer-reviewed)abstract
- Objectives To describe the clinical history and ultrasound findings in women with decidualized endometriomas surgically removed during pregnancy. Methods In this retrospective study, women with a histological diagnosis of decidualized endometrioma during pregnancy who had undergone preoperative ultrasound examination were identified from the databases of seven ultrasound centers. The ultrasound appearance of the tumors was described on the basis of ultrasound images, ultrasound reports and research protocols (when applicable) by one author from each center using the terms and definitions of the International Ovarian Tumor Analysis (IOTA) group. In addition, two authors reviewed together available digital ultrasound images and used pattern recognition to describe the typical ultrasound appearance of decidualized endometriomas. Results Eighteen eligible women were identified. Median age was 34 (range, 20-43) years. Median gestational age at surgical removal of the decidualized endometrioma was 18 (range, 11-41) weeks. Seventeen women (94%) were asymptomatic and one presented with pelvic pain. In three of the 18 women an ultrasound diagnosis of endometrioma had been made before pregnancy. The original ultrasound examiner was uncertain whether the mass was benign or malignant in 10 (56%) women and suggested a diagnosis of benignity in nine (50%) women, borderline in eight women (44%), and invasive malignancy in one (6%) woman. Seventeen decidualized endometriomas contained a papillary projection, and in 16 of these at least one of the papillary projections was vascularized at power or color Doppler examination. The number of cyst locules varied between one (n=11) and four. No woman had ascites. When using pattern recognition, most decidualized endometriomas (14/17, 82%) were described as manifesting vascularized rounded papillary projections with a smooth contour in an ovarian cyst with one or a few cyst locules and ground-glass or low-level echogenicity of the cyst fluid. Conclusions Rounded vascularized papillary projections with smooth contours within an ovarian cyst with cyst contents of ground-glass or low-level echogenicity are typical of surgically removed decidualized endometriomas in pregnant women, most of whom are asymptomatic. Copyright (C) 2014 ISUOG. Published by John Wiley & Sons Ltd.
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| 5. |
- Testa, A, et al.
(author)
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Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study.
- 2014
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 111:4, s. 680-688
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Journal article (peer-reviewed)abstract
- Background:To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3.Methods:This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery.Results:The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917-0.942), 0.918 (0.905-0.930), 0.914 (0.886-0.936) and 0.875 (0.853-0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90-96%, specificity 74-79% and diagnostic odds ratio (DOR) 32.8-50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6-75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5.Conclusions:This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference.British Journal of Cancer advance online publication 17 June 2014; doi:10.1038/bjc.2014.333 www.bjcancer.com.
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| 6. |
- Valentin, Lil, et al.
(author)
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Adnexal masses difficult to classify as benign or malignant using subjective assessment of gray scale and Doppler ultrasound findings: logistic regression models do not help.
- 2011
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In: Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology. - : Wiley. - 1469-0705. ; 38:4, s. 456-465
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Journal article (peer-reviewed)abstract
- AIM: To develop a logistic regression model that can discriminate between benign and malignant adnexal masses perceived to be difficult to classify by subjective evaluation of gray scale and Doppler ultrasound findings (subjective assessment) and to compare its diagnostic performance with that of subjective assessment, serum CA 125 and the risk of malignancy index (RMI). METHODS: We used the 3511 patients with an adnexal mass included in the International Ovarian Tumor Analysis (IOTA) studies. All patients had been examined with transvaginal gray scale and Doppler ultrasound following a standardized research protocol by an experienced ultrasound examiner using a high end ultrasound system. In addition to prospectively collecting information on > 40 clinical and ultrasound variables, the ultrasound examiner classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for the unclassifiable masses (n = 244, i.e. 7% of all tumors) using a training set (160 tumors, 45 malignancies) and then tested on a test set (84 tumors, 28 malignancies). The gold standard was the histological diagnosis of the surgically removed adnexal mass. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive and negative likelihood ratio (LR+, LR-) were used to describe diagnostic performance and were compared between subjective assessment, CA 125, the RMI and the logistic regression model created. RESULTS: One variable was retained in the logistic regression model: the largest diameter (in mm) of the largest solid component of the tumor (OR 1.04, 95% CI 1.02 - 1.06). The model had an AUC of 0.68 (95% confidence interval, CI 0.59 to 0.78) on the training set and 0.65 (95%CI 0.53 to 0.78) on the test set. On the test set, a cutoff of 25% probability of malignancy (corresponding to largest diameter of largest solid component 23mm) resulted in sensitivity 64% (18/28), specificity 55% (31/56), LR+ 1.44 and LR- 0.65. The corresponding figures for subjective assessment were 68% (19/28), 59% (33/56), 1.65 and 0.55. On the test set of patients with available CA 125 results, the LR+ and LR- of the logistic regression model (cutoff 25% probability of malignancy) were 1.29 and 0.73, of subjective assessment 1.44 and 0.63, of CA 125 (cutoff 35 U/mL) 1.25 and 0.84 and of RMI (cutoff 200) 1.21 and 0.92. CONCLUSION: About 7% of adnexal masses that are considered appropriate to remove surgically cannot be classified as benign or malignant by experienced ultrasound examiners using subjective assessment. Logistic regression models to estimate the risk of malignancy, CA 125 measurements and the RMI are not helpful in these masses. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.
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| 7. |
- Valentin, Lil, et al.
(author)
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Unilocular adnexal cysts with papillary projections but no other solid components: is there a diagnostic method that can reliably classify them as benign or malignant before surgery?
- 2013
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 41:5, s. 570-581
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Journal article (peer-reviewed)abstract
- Aim: To develop a logistic regression model for discrimination between benign and malignant unilocular solid cysts with papillary projections but no other solid components, and to compare its diagnostic performance with that of subjective evaluation of ultrasound findings (subjective assessment), CA 125 and the risk of malignancy index (RMI). Methods: Among the 3511 adnexal masses in the International Ovarian Tumor Analysis (IOTA) database there were 252 (7%) unilocular solid cysts with papillary projections but no other solid components ('unilocular cysts with papillations'). All had been examined with transvaginal ultrasound using the IOTA standardized research protocol. The ultrasound examiner also classified each mass as certainly or probably benign, unclassifiable, or certainly or probably malignant. A logistic regression model to discriminate between benignity and malignancy was developed for all unilocular cysts with papillations (175 tumors in training set, 77 in test set) and for unilocular cysts with papillations where the ultrasound examiner was not certain about benignity/malignancy (113 tumors in training set, 53 in test set). The gold standard was the histological diagnosis of the surgically removed adnexal mass. Results: A model containing six variables was developed for all unilocular cysts with papillations. The model had an area under the receiver operating characteristic curve (AUC) on the test set of 0.83 (95% CI, 0.74-0.93). The optimal risk cutoff as defined on the training set (0.35) resulted in sensitivity 69% (20/29), specificity 83% (40/48), LR+ 4.14 and LR- 0.37 on the test set. The corresponding values for subjective assessment when using the ultrasound examiner's dichotomous classification of the mass as benign or malignant were 97% (28/29), 79% (38/48), 4.63 and 0.04. A model containing four variables was developed for unilocular cysts with papillations where the ultrasound examiner was not certain about benignity/malignancy. The model had an AUC of 0.74 (95% CI, 0.60-0.88) on the test set. The optimal risk cutoff of the model as defined on the training set (0.30) resulted in sensitivity 62% (13/21), specificity 72% (23/32), LR+ 2.20 and LR- 0.53 on the test set. The corresponding values for subjective assessment were 95% (20/21), 78% (25/32), 4.35 and 0.06. CA125 and RMI had virtually no diagnostic ability. Conclusion: Even though logistic regression models to predict malignancy in unilocular cysts with papillations can be developed they have at most moderate performance and are not superior to subjective assessment for discrimination between benignity and malignancy. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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| 8. |
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| 9. |
- Zannoni, L, et al.
(author)
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Intra- and inter-observer reproducibility of assessment of Doppler ultrasound findings in adnexal masses.
- 2013
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In: Ultrasound in Obstetrics & Gynecology. - : Wiley. - 1469-0705 .- 0960-7692. ; 42:1, s. 93-101
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Journal article (peer-reviewed)abstract
- Objectives: To estimate intra- and inter-observer reproducibility and reliability of assessment of the color content in adnexal masses at color/power Doppler ultrasound examination for observers with different levels of experience, and to determine if they change after a consensus meeting. Methods: Digital clips with color/power Doppler information of 103 adnexal masses were evaluated independently four times, twice before and twice after a consensus meeting, by four experienced and three less experienced ultrasound examiners. The color content of the adnexal mass was estimated using the International Ovarian Tumor Analysis color score and a 100 mm visual analogue scale (VAS score). Intraobserver repeatability was estimated for each observer. Interobserver agreement was estimated for the four most experienced observers (six pairs), for the three less experienced observers (three pairs), and for four other pairs of observers, each pair consisting of one of the experienced and one of the less-experienced observers. Results: Intra- and inter-observer agreement for the color score was moderate to very good, percentage agreement ranging from 48% to 82.5% (Kappa 0.52-0.82) before and from 59% to 90% (Kappa 0.60-0.88) after the consensus meeting. For seven of 13 pairs of observers, interobserver agreement improved after the consensus meeting. Intra-observer intraclass correlation coefficient (ICC) values for the VAS score ranged from 0.80 to 0.92 before and from 0.75 to 0.94 after the consensus meeting, but limits of agreement were wide (+/-20-35 mm). For six of the seven observers the ICC values were higher after the consensus meeting than before. Inter-observer ICC values for the VAS score ranged from 0.77 to 0.88 before and from 0.77 to 0.91 after the consensus meeting, but limits of agreement were wide (+/-30-40 mm). For ten of 13 pairs of observers the ICC values improved after the consensus meeting. Conclusions: Intra-and inter-observer agreement for the color score was good, especially after the consensus meeting, but there is room for improvement. VAS score results varied substantially within and between observers both before and after the consensus meeting. General consensus needs to be reached about how to interpret color/power Doppler ultrasound findings in adnexal masses. Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
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| 10. |
- Berg, Sylvia, et al.
(author)
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Iceland's best kept secret
- 2014
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In: Geology Today. - : Wiley. - 0266-6979 .- 1365-2451. ; 30:2, s. 54-60
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Journal article (peer-reviewed)abstract
- The ‘forgotten fjords’ and ‘deserted inlets’ of NE-Iceland, in the region between Borgarfjörður Eystri and Loðmundarfjörður, are not only prominent because of their pristine landscape, their alleged elfin settlements, and the puffins that breed in the harbour, but also for their magnificent geology. From a geological point of view, the area may hold Iceland's best kept geological secret. The greater Borgarfjörður Eystri area hosts mountain chains that consist of voluminous and colourful silicic rocks that are concentrated within a surprisingly small area (Fig. 1), and that represent the second-most voluminous occurrence of silicic rocks in the whole of Iceland. In particular, the presence of unusually large volumes of ignimbrite sheets documents extremely violent eruptions during the Neogene, which is atypical for this geotectonic setting. As a group of geoscientists from Uppsala University (Sweden) and the Nordic Volcanological Center (NordVulk, Iceland) we set out to explore this remote place, with the aim of collecting material that may allow us to unravel the petrogenesis of these large volumes of silicic rocks. This effort could provide an answer to a long-standing petrological dilemma; the question of how silicic continental crust is initially created. Here we document on our geological journey, our field strategy, and describe our field work in the remote valleys of NE-Iceland.
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