Objectives Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic... Show moreObjectives Thrombus computed tomography (CT) characteristics might be used to assess histopathologic thrombus composition in patients treated with endovascular thrombectomy (EVT) for acute ischemic stroke (AIS). We aimed to assess the variability in thrombus composition that could be predicted with combined thrombus CT characteristics. Methods Thrombi of patients enrolled in the MR CLEAN Registry between March 2014 and June 2016 were histologically analyzed with hematoxylin-eosin staining and quantified for percentages of red blood cells (RBCs) and fibrin/platelets. We estimated the association between general qualitative characteristics (hyperdense artery sign [HAS], occlusion location, clot burden score [CBS]) and thrombus composition with linear regression, and quantified RBC variability that could be explained with individual and combined characteristics with R-2. For patients with available thin-slice (<= 2.5 mm) imaging, we performed similar analyses for general and quantitative characteristics (HAS, occlusion location, CBS, [relative] thrombus density, thrombus length, perviousness, distance from ICA-terminus). Results In 332 included patients, the presence of HAS (a beta 7.8 [95% CI 3.9-11.7]) and shift towards a more proximal occlusion location (a beta 3.9 [95% CI 0.6-7.1]) were independently associated with increased RBC and decreased fibrin/platelet content. With general characteristics, 12% of RBC variability could be explained; HAS was the strongest predictor. In 94 patients with available thin-slice imaging, 30% of RBC variability could be explained; thrombus density and thrombus length were the strongest predictors. Conclusions Quantitative thrombus CT characteristics on thin-slice admission CT improve prediction of thrombus composition and might be used to further guide clinical decision-making in patients treated with EVT for AIS in the future. Show less
Purpose To evaluate the magnetic resonance imaging (MRI) characteristics of uveal melanoma (UM), to compare them with fundoscopy and ultrasound (US), and to validate them with histopathology.... Show morePurpose To evaluate the magnetic resonance imaging (MRI) characteristics of uveal melanoma (UM), to compare them with fundoscopy and ultrasound (US), and to validate them with histopathology. Methods MR images from 42 UM were compared with US and fundoscopy, and on 14 enucleated cases with histopathology. Results A significant relationship between the signal intensity on T1 and pigmentation on histopathology was found (p=0.024). T1 hyperintense UM were always moderately or strongly pigmented on histopathology, while T1-hypointense UM were either pigmented or non-pigmented. Mean apparent diffusion coefficient (ADC) of the UM was 1.16 +/- 0.26 x 10(-3) mm(2)/s. Two-thirds of the UM had a wash-out and the remaining a plateau perfusion time-intensity curve (TIC). MRI was limited in evaluating the basal diameter of flat tumors. US tends to show larger tumor prominence (0.5mm larger, p=0.008) and largest basal diameter (1.4mm larger, p<0.001). MRI was good in diagnosing ciliary body involvement, extrascleral extension, and optic nerve invasion, but limited on identifying scleral invasion. An increase of tumor prominence was associated with lower ADC values (p=0.030) and favored a wash-out TIC (p=0.028). An increase of tumor ADC correlated with a plateau TIC (p=0.011). Conclusions The anatomical and functional MRI characteristics of UM were comprehensively assessed. Knowing the MRI characteristics of UM is important in order to confirm the diagnosis and to differentiate UM from other intra-ocular lesions and because it has implications for treatment planning. MRI is a good technique to evaluate UM, being only limited in case of flat tumors or on identifying scleral invasion. Show less
Rutgers, J.J.; Banki, T.; Kamp, A. van der; Waterlander, T.J.; Scheijde-Vermeulen, M.A.; Heuvel-Eibrink, M.M. van den; ... ; Krijger, R.R. de 2021
Background Histopathological classification of Wilms tumors determines treatment regimen. Machine learning has been shown to contribute to histopathological classification in various malignancies... Show moreBackground Histopathological classification of Wilms tumors determines treatment regimen. Machine learning has been shown to contribute to histopathological classification in various malignancies but requires large numbers of manually annotated images and thus specific pathological knowledge. This study aimed to assess whether trained, inexperienced observers could contribute to reliable annotation of Wilms tumor components for classification performed by machine learning. Methods Four inexperienced observers (medical students) were trained in histopathology of normal kidneys and Wilms tumors by an experienced observer (pediatric pathologist). Twenty randomly selected scanned Wilms tumor-slides (from n = 1472 slides) were annotated, and annotations were independently classified by both the inexperienced observers and two experienced pediatric pathologists. Agreement between the six observers and for each tissue element was measured using kappa statistics (kappa). Results Pairwise interobserver agreement between all inexperienced and experienced observers was high (range: 0.845-0.950). The interobserver variability for the different histological elements, including all vital tumor components and therapy-related effects, showed high values for all kappa-coefficients (> 0.827). Conclusions Inexperienced observers can be trained to recognize specific histopathological tumor and tissue elements with high interobserver agreement with experienced observers. Nevertheless, supervision by experienced pathologists remains necessary. Results of this study can be used to facilitate more rapid progress for supervised machine learning-based algorithm development in pediatric pathology and beyond. Show less
Ductal carcinoma in situ (DCIS) is considered to be a non-obligate precursor of invasive breast cancer (IBC). Optimal clinical management of DCIS remains controversial, as we are unable to... Show moreDuctal carcinoma in situ (DCIS) is considered to be a non-obligate precursor of invasive breast cancer (IBC). Optimal clinical management of DCIS remains controversial, as we are unable to identify those DCIS lesions with invasive potential. As a result, current treatment guidelines for DCIS dictate that all women diagnosed with DCIS should undergo treatment to prevent the development of IBC. This makes that many women, who have a low-risk to develop subsequent IBC, are being harmed by this intensive treatment without any benefit. Furthermore, definite proof of DCIS progression to IBC is still lacking.The objectives of this thesis were to identify prognostic markers predictive of the development of subsequent ipsilateral IBC after DCIS and to explore the clonal relatedness of patient-matched DCIS and subsequent ipsilateral IBC. To achieve this, histopathological analysis and molecular profiling were performed using a patient group which was part of a nation-wide population-based cohort including all women diagnosed with and treated for DCIS with breast conserving surgery alone in the Netherlands between 1989 and 2005. The results presented in this thesis will help to stratify a woman’s individual risk of subsequent invasive breast cancer development and will help to avoid overtreatment. Show less
Aims: Chronic-active antibody mediated rejection (c-aABMR) is a major cause of kidney graft loss. Currently, little is known about the relation between histopathologic parameters and renal... Show moreAims: Chronic-active antibody mediated rejection (c-aABMR) is a major cause of kidney graft loss. Currently, little is known about the relation between histopathologic parameters and renal allograft survival.Methods and results: Between 2008 and 2014, 41 patients with a progressive decrease in renal function were diagnosed with c-aABMR according to Banff 2015 and followed up for at least 3 years. Clinical and renal biopsy characteristics were analyzed for association with graft survival.During follow-up 26 cases lost their graft because of c-aABMR at a median follow up of 40 months after diagnosis.Cases with v-lesions in their biopsy had a significant higher loss of eGFR prior to diagnosis. The total inflammation score (r = -0.45 p = .007) and the severity of interstitial fibrosis (r = -0.38 p = .023) were related to the eGFR at time of biopsy.Univariate regression analysis showed that eGFR at time of biopsy, total inflammation, interstitial fibrosis and the sum chronicity score were significantly related to the risk for graft failure during follow-up. In a multivariate analysis only the severity of interstitial fibrosis remained associated with decreased graft survival (HR 1.9 per score point, 95% CI 1.2-2.8, p = .004).Conclusion: Severity of renal interstitial fibrosis and not inflammation predicts graft survival in cases of c-aABMR. Show less
Prostate cancer (PCa) is frequently treated with radiotherapy. However, depending on the aggressiveness of the disease, the risk of recurrence can be up to 35% within five years of the initial... Show moreProstate cancer (PCa) is frequently treated with radiotherapy. However, depending on the aggressiveness of the disease, the risk of recurrence can be up to 35% within five years of the initial treatment. Patients with localised recurrent PCa are candidates for curative (i.e. salvage) treatment. To overcome the toxicity associated with whole-gland approaches, focal salvage treatments target the index lesion while sparing the surrounding tissue. The studies described in this thesis elaborate on the use of quantitative multi-parametric MRI (mp-MRI) for the detection and localisation of locally recurrent PCa after radiotherapy. Pre-treatment radiomic imaging features were found to have potential to improve recurrence-risk prediction models for high-risk PCa patients treated with radiotherapy. In this thesis, the mp-MRI properties of irradiated benign tissue and recurrent tumour were characterised, with access to pathological samples. These findings can be used as a foundation to establish guidelines (which are currently absent) on how to assess and score MRI scans after radiotherapy. Improving radiological knowledge in the recurrent setting can lead to improved staging and result in better patient selection for salvage treatments. Lastly, this thesis provides evidence on how best to define the region to target, leading to a refinement of focal salvage strategies. Show less
Grewal, N.; Girdauskas, E.; DeRuiter, M.; Goumans, M.J.; Poelmann, R.E.; Klautz, R.J.M.; Gittenberger-de Groot, A.C. 2019
Background: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation and is associated with ascending aortic dilation in 60%-80% of patients. In this study, we aimed to... Show moreBackground: A bicuspid aortic valve (BAV) is the most common congenital cardiac malformation and is associated with ascending aortic dilation in 60%-80% of patients. In this study, we aimed to address the role of hemodynamic influences on the development of aortopathy in BAV patients.Patient and methods: BAV (n=36) and tricuspid aortic valve (TAV) patients (n=17) undergoing aortic valve replacement underwent preoperative flow magnetic resonance imaging (MRI) assessment to detect the area of maximal flow-induced stress in the proximal aorta. Based on these MRI data, paired ascending aortic wall samples [i.e., area of maximal jet impact (jet sample) and the opposite aortic wall (nonjet sample)] were collected during surgery. To study and describe the effects of jet stream on the complete vascular wall, a pathology score was developed based on the recently published aortic consensus paper statement on surgical pathology of the aorta using routine histologic stainings (resorcin fuchsin, hematoxylin-eosin, and Movat) and immunohistochemistry (alpha smooth muscle actin, smooth muscle 22 alpha, platelet endothelial cell adhesion molecule).Results: Comparing the jet and nonjet samples in both BAV and TAV, regions of maximal jet impact did not show any difference in the pathology score in the adventitia and the middle and outer media. In the jet samples, the inner media however showed loss of actin expression in both BAV (P<.0001) and the TAV (P=.0074), and the intimal thickness was significantly enlarged in both patient groups (BAV P=.0005, TAV P=.0041), which was not accompanied by loss of elastic lamellae or vascular smooth muscle cell nuclei.Conclusions: In our study population, we could not demonstrate a potential distinct role for hemodynamics in the development of aortopathy in BAV patients even if corrected for aortic diameter, raphe position, or whether the valve is stenotic or regurgitant. The intimal layer and inner media however showed alterations in all jet specimens. (C) 2019 The Authors. Published by Elsevier Inc. Show less
Purpose: Improve mapping and registration of longitudinal view on histopathology vessels in a three-dimensional alignment procedure for postmortem quantitative coronary plaque analyses. This new... Show morePurpose: Improve mapping and registration of longitudinal view on histopathology vessels in a three-dimensional alignment procedure for postmortem quantitative coronary plaque analyses. This new procedure is applied and results shown using calcified coronary plaque analyses within post-mortem computed tomography angiography (PMCTA), optical coherence tomography (OCT) and the gold standard of histopathology.Results: In total, 338 annotated histopathology images were included, 166 PMCTA transversal images and 285 OCT images were aligned in the comparison. The results from the comparison using the alignment procedure showed overall that the calcified plaques seem to be overestimated by PMCTA and underestimated by OCT.Conclusions: The 3D fusion approach, aligning the images of PMCTA, OCT and histopathology as gold standard allowed for a slice-based comparison of the different modalities. The results showed that PMCTA overestimates the calcified plaques while OCT underestimates these, compared to histopathology. (C) 2018 Elsevier Inc. All rights reserved. Show less
ANCA-associated vasculitis (AAV) describes a group of small-vessel vasculitides with frequent renal involvement. The first description of these conditions can be traced back to the 19th-century... Show moreANCA-associated vasculitis (AAV) describes a group of small-vessel vasculitides with frequent renal involvement. The first description of these conditions can be traced back to the 19th-century paper on necrotizing vasculitis by Kussmaul and Maier. Since then, our understanding of the pathogenesis has improved and the histopathological lesions have been described in detail. Characteristic histologic lesions in ANCA-associated glomerulonephritis (AAGN) are fibrinoid necrosis and crescents, often accompanied by tubulointerstitial inflammation. The discovery of ANCAs has not rendered renal biopsies obsolete in the diagnostic process. Currently, renal biopsies remain the gold standard for the diagnosis of AAV in conjunction with ANCA serology. In addition to diagnosis, renal biopsies are useful for patient prognosis. The evaluation of renal histological samples from patients with new-onset AAV who participated in clinical trials led to the proposal of the histopathological classification for AAGN. The prognostic value of this classification continues to be validated and an update is expected soon. (C) 2018 Elsevier Ltd. All rights reserved. Show less
Halushka, M.K.; Angelini, A.; Bartoloni, G.; Basso, C.; Batoroeva, L.; Bruneval, P.; ... ; Wal, A.C. van der 2016
Primair cutane B-cel lymfomen (CBCL) vormen een heterogene groep van non-Hodgkin lymfomen die zich primair in de huid manifesteren zonder aanwezigheid van extracutane lokalisaties. Volgens de in... Show morePrimair cutane B-cel lymfomen (CBCL) vormen een heterogene groep van non-Hodgkin lymfomen die zich primair in de huid manifesteren zonder aanwezigheid van extracutane lokalisaties. Volgens de in Nederland toegepaste EORTC-classificatie kunnen 3 typen CBCL onderscheiden worden: het primair cutaan immunocytoom of marginale zone B-cel lymfoom, het primair cutaan follikelcentrumcel lymfoom en het primair cutaan grootcellig B-cel lymfoom van het been. De studies in dit proefschrift hebben door middel van clinicopathologisch onderzoek en verschillende moleculair biologische technieken (waaronder genexpressie analyse, array-CGH en FISH-analyse) geresulteerd in de identificatie van een aantal nieuwe diagnostische en prognostische markers en daarnaast specifieke genetische kenmerken van de verschillende typen CBCL aangetoond. Deze resultaten hebben in de eerste plaats geleid tot een betere definitie van de verschillende typen CBCL. Daarnaast hebben de resultaten van deze studies een belangrijke rol gespeeld in de totstandkoming van een nieuwe consensus classificatie voor cutane lymfomen in 2005. In deze WHO-EORTC classificatie worden de volgende 3 belangrijkste typen CBCL onderscheiden: het primair cutaan marginale zone B-cel lymfoom, het primair cutaan follikelcentrum lymfoom en het primair cutaan grootcellig B-cel lymfoom, been type. Show less
