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.
Groenveld R.L.,Spectrum |
Raber M.H.,Spectrum |
Oosterhof-Berktas R.,Spectrum |
Eijken E.,Laboratorium Pathologie Oost Nederland |
Case Reports in Gastroenterology | Year: 2014
A 28-year-old woman was referred to our hospital because of abdominal pain, weight loss and a palpable intra-abdominal mass. A CT scan revealed a tumor with a diameter of 7 cm with sharp margins, intra-tumoral fatty components and enhancing soft tissue. After initial workup, which suggested an inflammatory myofibroblastic tumor (IMT), she underwent laparotomy with complete resection. Pathological examination indeed revealed IMT. IMT is a rare benign neoplasm and has been described in nearly the entire body. It presents with nonspecific symptoms. The therapy of abdominal IMT consists of radical surgery because of high local recurrence rates. In this case report clinical, surgical, radiological and histological features with a review of the relevant literature are described. © 2014 S. Karger AG, Basel.
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.
Seidel K.,University of Groningen |
Seidel K.,Goethe University Frankfurt |
Den Dunnen W.F.A.,University of Groningen |
Schultz C.,Goethe University Frankfurt |
And 8 more authors.
Acta Neuropathologica | Year: 2010
Protein aggregation is a major pathological hallmark of many neurodegenerative disorders including polyglutamine diseases. Aggregation of the mutated form of the disease protein ataxin-3 into neuronal nuclear inclusions is well described in the polyglutamine disorder spinocerebellar ataxia type 3 (SCA3 or Machado-Joseph disease), although these inclusions are not thought to be directly pathogenic. Neuropil aggregates have not yet been described in SCA3. We performed a systematic immunohistochemical study of serial thick sections through brains of seven clinically diagnosed and genetically confirmed SCA3 patients. Using antibodies against ataxin-3, p62, ubiquitin, the polyglutamine marker 1C2 as well as TDP-43, we analyzed neuronal localization, composition and distribution of aggregates within SCA3 brains. The analysis revealed widespread axonal aggregates in fiber tracts known to undergo neurodegeneration in SCA3. Similar to neuronal nuclear inclusions, the axonal aggregates were ubiquitinated and immunopositive for the proteasome and autophagy associated shuttle protein p62, indicating involvement of neuronal protein quality control mechanisms. Rare TDP-43 positive axonal inclusions were also observed. Based on the correlation between affected fiber tracts and degenerating neuronal nuclei, we hypothesize that these novel axonal inclusions may be detrimental to axonal transport mechanisms and thereby contribute to degeneration of nerve cells in SCA3. © 2010 Springer-Verlag.
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.
Edelbroek J.R.,Leiden University |
Vermeer M.H.,Leiden University |
Jansen P.M.,Leiden University |
Stoof T.J.,VU University Amsterdam |
And 3 more authors.
British Journal of Dermatology | Year: 2012
Background Langerhans cell histiocytosis (LCH) in adults first presenting in the skin is rare. Guidelines for staging, treatment and follow-up are lacking. Objectives To better define staging procedures, treatment results and clinical course in adult patients with LCH first presenting in the skin. Methods Eighteen adult patients with LCH first presenting in the skin were collected from five centres collaborating in the Dutch Cutaneous Lymphoma Group. Clinical records and (skin) biopsy specimens were reviewed and follow-up data were obtained. A literature search on adult patients with LCH presenting in the skin was performed. Results Staging procedures showed extracutaneous disease in three of 16 patients who were adequately staged. One patient had a histologically confirmed lytic LCH bone lesion, while two patients had a myelodysplastic syndrome. During follow-up two of 18 patients developed extracutaneous localizations of LCH. Five patients developed a second haematological malignancy, including (myelo)monocytic leukaemia (two cases), histiocytic sarcoma (one case), diffuse large B-cell lymphoma (one case) and peripheral T-cell lymphoma (one case). Review of the literature revealed six other adult patients with a second haematological malignancy preceding or following a diagnosis of LCH. Conclusions The results of the present study suggest an increased risk of a second haematological malignancy in adult patients with LCH presenting in the skin. Extensive staging at presentation and long-term follow-up are therefore warranted in such patients. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.
PubMed | Spectrum and Laboratorium Pathologie Oost Nederland
Type: Journal Article | Journal: Gastroenterology research | Year: 2016
A 67 year old female was referred because of an incidentaloma on CT-scan and MRI which showed a 5.0 cm large mass in the wall of the distal stomach. After an initial work-up which suggested a gastrointestinal stromal tumor (GIST), a partial gastrectomy with a Billroth II gastrojejunostomy was performed. The histological diagnosis was a schwannoma. Gastric schwannomas are rare tumors which comprise 0.2% of all gastric tumors and 4% of all benign gastric neoplasms with a peak of incidence in the 4th and 5th decade of life. Gastric schwannomas are usually asymptomatic, but can present with ulceration and/or gastrointestinal bleeding. Clinical, endoscopical, surgical, radiological and histological features of this case are described and the relevant literature is reviewed.
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.
PubMed | TU Munich, Laboratorium Pathologie Oost Nederland, University of Twente and MESA Institute for Nanotechnology
Type: | Journal: Scientific reports | Year: 2016
The formation of -synuclein (-S) amyloid aggregates, called Lewy bodies (LBs), is a hallmark of Parkinsons disease (PD). The function of LBs in the disease process is however still unclear; they have been associated with both neuroprotection and toxicity. To obtain insight into this contradiction, we induced the formation of -S inclusions, using three different induction methods in SH-SY5Y cells and rat-derived primary neuronal cells. Using confocal and STED microscopy we observed induction-dependent differences in -S inclusion morphology, location and function. The aggregation of -S in functionally different compartments correlates with the toxicity of the induction method measured in viability assays. The most cytotoxic treatment largely correlates with the formation of proteasome-associated, juxta-nuclear inclusions. With less toxic methods cytosolic deposits that are not associated with the proteasome are more prevalent. The distribution of -S over at least two different types of inclusions is not limited to cell models, but is also observed in primary neuronal cells and in human mesencephalon. The existence of functionally different LBs, in vivo and in vitro, gives important insights in the impact of Lewy Body formation on neuronal functioning and may thereby provide a platform for discovering therapeutics.
PubMed | University of Twente and Laboratorium Pathologie Oost Nederland
Type: | Journal: Scientific reports | Year: 2015
Hepatic stellate cells (HSCs) known as master producers and macrophages as master regulators, are the key cell types that strongly contribute to the progression of liver fibrosis. Since Notch signaling regulates multiple cellular processes, we aimed to study the role of Notch signaling in HSCs differentiation and macrophages polarization and to evaluate its implication in liver fibrogenesis. Notch pathway components were found to be significantly upregulated in TGF-activated HSCs, inflammatory M1 macrophages, and in mouse and human fibrotic livers. Interestingly, inhibition of Notch using a selective -secretase inhibitor, Avagacestat, significantly inhibited TGF-induced HSC activation and contractility, and suppressed M1 macrophages. Additionally, Avagacestat inhibited M1 driven-fibroblasts activation and fibroblasts-driven M1 polarization (nitric oxide release) in fibroblasts and macrophages co-culture, and conditioned medium studies. In vivo, post-disease treatment with Avagacestat significantly attenuated fibrogenesis in CCl4-induced liver fibrosis mouse model. These effects were attributed to the reduction in HSCs activation, and inhibition of inflammatory M1 macrophages and upregulation of suppressive M2 macrophages. These findings suggest that Notch signaling plays a crucial role in HSC activation and M1/M2 polarization of macrophages in liver fibrosis. These results provide new insights for the development of novel therapies against liver fibrosis through modulation of Notch signaling.