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  • Van Holsbeke, C., et al. (författare)
  • Prospective external validation of the 'ovarian crescent sign' as a single ultrasound parameter to distinguish between benign and malignant adnexal pathology
  • 2010
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - John Wiley & Sons. - 1469-0705. ; 36:1, s. 81-87
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To determine the sensitivity and specificity of the 'ovarian crescent sign' (OCS) - a rim of normal ovarian tissue seen adjacent to an ipsilateral adnexal mass as a sonographic feature to discriminate between benign and malignant adnexal masses. Methods The patients included were a subgroup of patients participating in the International Ovarian Tumor Analysis (IOTA) Phase 2 study, which is an international multicenter study. The subgroup comprised 1938 patients, with an adnexal mass, recruited from 19 ultrasound centers in different countries. All patients were scanned using the same standardized ultrasound protocol. Information on more than 40 demographic and ultrasound variables were collected, but the evaluation of the OCS was optional. Only patients from centers that had evaluated the OCS in >= 90% of their cases were included. The gold standard was the histological diagnosis of the adnexal mass. The ability of the OCS to discriminate between borderline or invasively malignant vs. benign adnexal masses, as well as between invasively malignant vs. other (benign and borderline) tumors, was determined and compared with the performance of subjective evaluation of ultrasound findings by the ultrasound examiner. Results The OCS was evaluated in 1377 adnexal masses from 12 centers, 938 (68%) masses being benign, 86 (6%) borderline, 305 (22%) primary invasive and 48 (3%) metastases. The OCS was present in 398 (42%) of 938 benign masses, in 14 (16%) of 86 borderline tumors, in 18 (6%) of 305 primary invasive tumors (one malignant struma ovarii, one uterine clear cell adenocarcinoma and 16 epithelial carcinomas, i.e. four Stage I and 12 Stage II-IV) and in two (4%) of 48 ovarian metastases. Hence, the sensitivity and specificity for absent OCS to identify a malignancy was 92% and 42%, respectively, and the positive and negative likelihood ratios (LR+ and LR-, respectively) were 1.60 and 0.18. Subjective impression performed significantly better than the OCS. Sensitivity and specificity were 90% and 92%, respectively, LR+ was 11.0 and LR- was 0.10. For discrimination between invasive vs. benign or borderline tumors, the sensitivity for absent OCS was 94%, the specificity was 40%, the LR+ was 1.58 and the LR- was 0.14. Conclusion This study confirms previous reports that the presence of the OCS decreases the likelihood of invasive malignancy in adnexal masses. However it is a poor discriminator between benign and malignant adnexal masses. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.
  • Van Holsbeke, Caroline, et al. (författare)
  • Prospective Internal Validation of Mathematical Models to Predict Malignancy in Adnexal Masses: Results from the International Ovarian Tumor Analysis Study
  • 2009
  • Ingår i: Clinical Cancer Research. - American Association for Cancer Research. - 1078-0432. ; 15:2, s. 684-691
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To prospectively test the mathematical models for calculation of the risk of malignancy in adnexal masses that were developed on the International Ovarian Tumor Analysis (IOTA) phase 1 data set on a new data set and to compare their performance with that of pattern recognition, our standard method. Methods: Three IOTA centers included 507 new patients who all underwent a transvaginal ultrasound using the standardized IOTA protocol. The outcome measure was the histologic classification of excised tissue. The diagnostic performance of 11 mathematical models that had been developed on the phase 1 data set and of pattern recognition was expressed as area under the receiver operating characteristic curve (AUC) and as sensitivity and specificity when using the cutoffs recommended in the studies where the models had been created. For pattern recognition, an AUC was made based on level of diagnostic confidence, Results: All IOTA models performed very well and quite similarly, with sensitivity and specificity ranging between 92% and 96% and 74% and 84%, respectively, and AUCs between 0.945 and 0.950. A least squares support vector machine with linear kernel and a logistic regression model had the largest AUCs. For pattern recognition, the AUC was 0.963, sensitivity was 90.2%, and specificity was 92.9%. Conclusion: This internal validation of mathematical models to estimate the malignancy risk in adnexal tumors shows that the IOTA models had a diagnostic performance similar to that in the original data set. Pattern recognition used by an expert sonologist remains the best method, although the difference in performance between the best mathematical model is not large.
  • Van Holsbeke, C., et al. (författare)
  • Real-time ultrasound vs. evaluation of static images in the preoperative assessment of adnexal masses
  • 2008
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - John Wiley & Sons. - 1469-0705. ; 32:6, s. 828-831
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To determine if the prediction of the Malignancy of all adnexal mass using pattern recognition, i.e. subjective evaluation of gray-scale and Doppler ultrasound findings, is as accurate when based on static images as it is when based on a real-time ultrasound examination. Methods The static images of 166 non-consecutive patients with 'difficult' adnexal masses, who all underwent surgery and for whom a histopathological diagnosis was available, were evaluated by three experts in gynecological ultrasound (image experts'). All ultrasound examinations bad been performed and the static images saved by a fourth expert sonologist ('real-time' sonologist). All four sonologists classified the adnexal masses as benign or malignant based on their subjective impression and stated with what degree of confidence their diagnosis was made. The diagnostic performance of the real-time sonologist was compared with that of each of The three image experts and with that of the 'consensus opinion' of the image experts (i.e. the diagnosis suggested by at least two of the latter). Results The real-time sonologist correctly predicted the diagnosis with an accuracy of 89% (148/166) vs. 85% (141/166) for the consensus opinion of static images (P = 0.0707). Equivalent values for sensitivity and specificity were 80% (56/170) vs. 83%, (58/70) (P = 0.4142) and 96%) (92/96) us. 86%, (83/96) (P = 0.0027), respectively. Conclusions The preoperative diagnosis of all adnexal mass made on the basis of a real-time ultrasound examination is more precise than a diagnosis made on the basis of saved static ultrasound images. Evaluation of static images is associated with lower diagnostic specificity. Copyright (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.
  • Van Holsbeke, Caroline, et al. (författare)
  • Ultrasound Experience Substantially Impacts on Diagnostic Performance and Confidence when Adnexal Masses Are Classified Using Pattern Recognition
  • 2010
  • Ingår i: Gynecologic and Obstetric Investigation. - Karger. - 1423-002X. ; 69:3, s. 160-168
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To determine how accurately and confidently examiners with different levels of ultrasound experience can classify adnexal masses as benign or malignant and suggest a specific histological diagnosis when evaluating ultrasound images using pattern recognition. Methods: Ultrasound images of selected adnexal masses were evaluated by 3 expert sonologists, 2 senior and 4 junior trainees. They were instructed to classify the masses using pattern recognition as benign or malignant, to state the level of confidence with which this classification was made and to suggest a specific histological diagnosis. Sensitivity, specificity, accuracy and positive and negative likelihood ratios (LR+ and LR-) with regard to malignancy were calculated. The area under the receiver operating characteristic curve (AUC) of pattern recognition was calculated by using six levels of diagnostic confidence. Results: 166 masses were examined, of which 42% were malignant. Sensitivity with regard to malignancy ranged from 80 to 86% for the experts, was 70 and 84% for the 2 senior trainees and ranged from 70 to 86% for the junior trainees. The specificity of the experts ranged from 79 to 91%, was 77 and 89% for the senior trainees and ranged from 59 to 83% for the junior trainees. The experts were uncertain about their diagnosis in 4-13% of the cases, the senior trainees in 15-20% and the junior trainees in 67-100% of the cases. The AUCs ranged from 0.861 to 0.922 for the experts, were 0.842 and 0.855 for the senior trainees, and ranged from 0.726 to 0.795 for the junior trainees. The experts suggested a correct specific histological diagnosis in 69-77% of the cases. All 6 trainees did so significantly less often (22-42% of the cases). Conclusion: Expert sonologists can accurately classify adnexal masses as benign or malignant and can successfully predict the specific histological diagnosis in many cases. Whilst less experienced operators perform reasonably well when predicting the benign or malignant nature of the mass, they do so with a very low level of diagnostic confidence and are unable to state the likely histology of a mass in most cases. Copyright (C) 2009 S. Karger AG, Basel
  • Van Holsbeke, C., et al. (författare)
  • Ultrasound methods to distinguish between malignant and benign adnexal masses in the hands of examiners with different levels of experience
  • 2009
  • Ingår i: Ultrasound in Obstetrics & Gynecology. - John Wiley & Sons. - 1469-0705. ; 34:4, s. 454-461
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To determine the effect of an ultrasound training course on the performance of pattern recognition when used by less experienced examiners and to compare the performance of pattern recognition, a logistic regression model and a scoring system to estimate the risk of malignancy between examiners with different levels of experience. Methods Using ultrasound images of selected adnexal masses, two trainees classified the masses as benign or malignant by using pattern recognition both before and after they bad attended a theoretical gynecological ultrasound course. They also classified the masses by using a logistic regression model and a scoring system, but only after they bad attended the course. The performance of these three methods when they were used by the trainees was then compared with that when they were used by experts. Results One hundred and sixty-five adnexal masses were included, of which 42% were malignant (21% invasive tumors and 21% borderline tumors). The area under the receiver- operating characteristics curve of pattern recognition when used by the trainees was similar before and after they had attended the course. Training decreased sensitivity (84% vs. 70% for Trainee 1, P = 0.004; 70% vs. 61% for Trainee2, P = 0.08) and increased specificity (77% vs. 92% for Trainee 1, P = 0.001; 89% vs. 95% for Trainee 2, P = 0.058). The performance of pattern recognition was poorer in the hands of the trainees than in the bands of the experts. The sensitivities of the logistic regression model were 70% and 54% for the trainees vs. 83% for an expert (P = 0.020 and < 0.001, respectively) and the specificities were 84% and 94% vs. 89% (P = 0.25 and 0.59, respectively). The sensitivities of the scoring system were 59% and 54% for the trainees vs. 75% for the expert (P = 0.002 and < 0.001, respectively), and the specificities were 90% and 93% vs. 85% (P = 0.103 and 0.008, respectively). Conclusion Theoretical ultrasound teaching did not seem to improve the performance of pattern recognition in the bands of trainees. A logistic regression model and a scoring system to classify adnexal masses as benign or malignant perform less well when they were used by inexperienced examiners than when used by an expert. Before using a model or a scoring system, experience and/or proper training are likely to be of paramount importance if diagnostic performance is to be optimized. Copyright (C) 2009 ISUOG. Published by John Wiley & Sons, Ltd.
  • van Hooren, Luuk, et al. (författare)
  • Local checkpoint inhibition of CTLA-4 as a monotherapy or in combination with anti-PD1 prevents the growth of murine bladder cancer
  • 2017
  • Ingår i: European Journal of Immunology. - 0014-2980 .- 1521-4141. ; 47:2, s. 385-393
  • Tidskriftsartikel (refereegranskat)abstract
    • Checkpoint blockade of CTLA-4 results in long-lasting survival benefits in metastatic cancer patients. However, patients treated with CTLA-4 blockade have suffered from immune-related adverse events, most likely due to the breadth of the induced T-cell activation. Here, we investigated the efficacy of a local low-dose anti-CTLA-4 administration for treatment of subcutaneous or orthotopic murine bladder 49 (MB49) bladder carcinoma in C57BL/6 mice. When MB49 tumors were grown s.c., peritumoral (p.t.) injection of anti-CTLA-4 treatment was equally effective as intravenous or s.c. (nontumor bearing flank) administration. Notably, p.t. injection was associated with lower circulating antibody levels and decreased IL-6 serum levels as compared to systemic treatment. Ultrasound-guided intratumoral anti-CTLA-4 antibody treatment of orthotopically growing MB49 tumors resulted in tumor regression, with more than tenfold reduction in systemic antibody levels as compared to i.v. or s.c. administration, in line with the compartmentally restrained nature of the bladder. Local anti-CTLA-4 therapy in combination with anti-PD-1 therapy resulted in complete responses, superior to each therapy alone. In addition, p.t. anti-CTLA-4 therapy was potentiated by depletion of regulatory T cells. Our results demonstrate that local anti-CTLA-4 antibody therapy is equally effective as systemic administration, but reduces systemic antibody levels and cytokine release, and enhances the response to anti-PD1 therapy.
  • Van Hul, M., et al. (författare)
  • Reduced obesity, diabetes, and steatosis upon cinnamon and grape pomace are associated with changes in gut microbiota and markers of gut barrier
  • 2018
  • Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - 0193-1849. ; 314:4, s. E334-E352
  • Tidskriftsartikel (refereegranskat)abstract
    • Increasing evidence suggests that polyphenols have a significant potential in the prevention and treatment of risk factors associated with metabolic syndrome. The objective of this study was to assess the metabolic outcomes of two polyphenol-containing extracts from cinnamon bark (CBE) and grape pomace (GPE) on C57BL/6J mice fed a high-fat diet (HFD) for 8 wk. Both CBE and GPK were able to decrease fat mass gain and adipose tissue inflammation in mice fed a HFD without reducing food intake. This was associated with reduced liver steatosis and lower plasma nonesterified fatty acid levels. We also observed a beneficial effect on glucose homeostasis, as evidenced by an improved glucose tolerance and a lower insulin resistance index. These ameliorations of the overall metabolic profile were associated with a significant impact on the microbial composition, which was more profound for the GPE than for the CBE. At the genus level. Peptococcus were decreased in the CBE group. In the GPE-treated group, several key genera that have been previously found to be linked with HFD, metabolic effects, and gut banter integrity were affected: we observed a decrease of Desulfovibrio, Lactococcus, whereas Allobaculum and Roseburia were increased. In addition, the expression of several antimicrobial peptides and tight junction proteins was increased in response to both CBK and GPH supplementation, indicating an improvement of the gut barrier function. Collectively, these data suggest that CBE and GPE can ameliorate the overall metabolic profile of mice on a high-fat diet, partly by acting on the gut microbiota.
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