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Jobsen J.J.,Spectrum | van der Palen J.,University of Twente | Ong F.,Spectrum | Riemersma S.,Laboratorium Pathologie Oost Nederland | Struikmans H.,Leiden University
Breast Cancer Research and Treatment | Year: 2015

The aims of this study were twofold: to analyze the incidence of patients having synchronous or metachronous bilateral invasive breast cancer (SBBC and MBBC) and to assess the characteristics and outcome compared to those having unilateral breast cancer (UBC). The used data were obtained from our prospective population-based cohort study which had been started in 1983. Bilateral breast cancer (BBC) was categorized as SBBC (≤3 months of the first primary) or MBBC (>3 months after the first primary). The incidence of SBBC was 1 % and that of MBBC 7.0 %. Patients with UBC showed more ductal carcinoma compared to patients with BBC. MBBC status was an independent significant predictor of local failure (HR 1.9; 95 % CI 1.3–2.7). SBBC status was an independent predictor of distant metastases (HR 2.6; 95 % CI 1.4–4.5). Overall survival (OS) was better for MBBC (HR 0.6; 95 % CI 0.4–0.8) and worse for SBBC (HR 2.3; 95 % CI 1.5–3.6) compared to UBC. We noted: (1) MBBC showed a significant higher local failure compared to UBC, (2) SBBC, compared to MBBC and UBC had a significant higher distant metastases rate, (3) disease-specific survival and OS were significantly worse for SBBC compared to UBC and MBBC, and (4) that the OS for MBBC compared to UBC, was significantly better. © 2015, Springer Science+Business Media New York. Source

Jobsen J.J.,Spectrum | Riemersma S.,Laboratorium Pathologie Oost Nederland | van der Palen J.,University of Twente | Ong F.,Spectrum | And 2 more authors.
European Journal of Surgical Oncology | Year: 2010

Purpose: The aim is to look at the impact of margin status and outcome of invasive lobular carcinoma (ILC) treated with breast-conserving therapy (BCT). Methods: This manuscript describes an analysis on 330 BCT in 318 patients with ILC. Results: The 12-year local relapse free survival (LRFS) is 89%. In multivariate analysis, positive margin status, age > 50 years, contra lateral breast cancer, and adjuvant systemic therapy were significant predictors of local relapse free survival. In a separate analysis limited to a positive margin for invasive carcinoma or carcinoma in situ, only a positive margin for invasive carcinoma was a significant predictor of local relapse free survival. This was limited to women ≤ 50 years. The 12-year disease-specific survival (DSS) was 85%. In multivariate Cox regression analysis grade 3 compared to grade 2 (HR 7.2), and a tumour size of pT2 (HR 2.5) were significant independent predictors of disease-specific survival (DFS). These factors were also relevant for distant metastasis-free survival (DMFS) and disease-free survival (DFS). Conclusions: Positive margins for invasive carcinoma seem to be a strong predictor for local recurrence in particular for women ≤ 50-years. Our study showed grade 3 and tumour size to be strong predictors of DMFS, DFS, and DSS. Margin status was not. © 2009 Elsevier Ltd. All rights reserved. Source

Chatterjea A.,University of Twente | Renard A.J.,Spectrum | Jolink C.,Laboratorium Pathologie Oost Nederland | van Blitterswijk C.A.,University of Twente | de Boer J.,University of Twente
Journal of Tissue Engineering and Regenerative Medicine | Year: 2012

Mesenchymal stromal cells are present in very low numbers in the bone marrow, necessitating their selective expansion on tissue culture plastic prior to their use in tissue-engineering applications. MSC expansion is laborious, time consuming, unphysiological and not economical, thus calling for automated bioreactor-based strategies. We and others have shown that osteogenic grafts can be cultured in bioreactors by seeding either 2D-expanded cells or by direct seeding of the mononuclear fraction of bone marrow. To further streamline this protocol, we assessed in this study the possibility of seeding the cells onto porous calcium phosphate ceramics directly from unprocessed bone marrow. Using predetermined volumes of bone marrow from multiple human donors with different nucleated cell counts, we were able to grow a confluent cell sheath on the scaffold surface in 3 weeks. Cells of stromal, endothelial and haematopoietic origin were detected, in contrast to grafts grown from 2D expanded cells, where only stromal cells could be seen. Upon implantation in nude mice, similar quantities of bone tissue were generated as compared to that obtained by using the conventional number of culture expanded cells from the same donor. We conclude that human osteogenic grafts can be efficiently prepared by direct seeding of cells from unprocessed bone marrow. © 2011 John Wiley & Sons, Ltd. Source

Scherzed W.,Goethe University Frankfurt | Brunt E.R.,University of Groningen | Heinsen H.,University of Wurzburg | De Vos R.A.,Laboratorium Pathologie Oost Nederland | And 10 more authors.
Cerebellum | Year: 2012

The cerebellum is one of the well-known targets of the pathological processes underlying spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3). Despite its pivotal role for the clinical pictures of these polyglutamine ataxias, no pathoanatomical studies of serial tissue sections through the cerebellum have been performed in SCA2 and SCA3 so far. Detailed pathoanatomical data are an important prerequisite for the identification of the initial events of the underlying disease processes of SCA2 and SCA3 and the reconstruction of its spread through the brain. In the present study, we performed a pathoanatomical investigation of serial thick tissue sections through the cerebellum of clinically diagnosed and genetically confirmed SCA2 and SCA3 patients. This study demonstrates that the cerebellar Purkinje cell layer and all four deep cerebellar nuclei consistently undergo considerable neuronal loss in SCA2 and SCA3. These cerebellar findings contribute substantially to the pathogenesis of clinical symptoms (i.e., dysarthria, intention tremor, oculomotor dysfunctions) of SCA2 and SCA3 patients and may facilitate the identification of the initial pathological alterations of the pathological processes of SCA2 and SCA3 and reconstruction of its spread through the brain. © Springer Science+Business Media, LLC 2011. Source

Ghebremedhin E.,Goethe University Frankfurt | Ghebremedhin E.,University of Queensland | Ghebremedhin E.,University of Ulm | Rosenberger A.,University of Gottingen | And 7 more authors.
Journal of Neuropathology and Experimental Neurology | Year: 2010

Cerebrovascular pathology is a major cause of stroke and mortality. Studies on prevalence of cerebrovascular pathologies in dementia with Lewy bodies (DLBs) and Parkinson disease (PD) patients are scarce and contradictory. We aimed to determine the prevalence and severity of cerebrovascular pathologies in DLB and PD and to analyze their relationship to LB pathology. The prevalence and severity of atherosclerosis in the circle of Willis, cerebral amyloid angiopathy, cerebral infarcts, hemorrhages, small-vessel disease, white matter lesions, including the Consortium to Establish a Registry for Alzheimer Disease (CERAD) protocol as well as Braak neurofibrillary tangle stages for AD pathology were analyzed in autopsy-verified DLB (n = 13), PD (n = 102), and control subjects (n = 53). In all patient groups, the extent of LB pathology was inversely correlated to the severity of most vascular pathologies (atherosclerosis, infarcts, and small-vessel disease; all p < 0.05). By contrast, cerebral amyloid angiopathy, CERAD, and Braak neurofibrillary tangle stages were positively correlated with LB pathology (p < 0.05). Whereas the overall prevalence and severity of small-vessel disease, infarcts, hemorrhages, and white matter lesions were comparable among both disease groups, the extents of atherosclerosis, cerebral amyloid angiopathy, CERAD, and Braak neurofibrillary tangle stages were significantly higher in DLB than in those of PD patients (p < 0.05). Microinfarcts were statistically more prevalent in each patient group than in controls, whereas gross infarcts predominated in controls (p < 0.05 each). In conclusion, DLB and PD patients with advanced LB pathology were less likely to show severe cerebrovascular disease or history of stroke. © 2010 by the American Association of Neuropathologists, Inc. Source

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