Vulvar cancer is a relatively rare gynaecologic malignancy with an annual incidence in developed countries of approximately 2 per 100,000 women. Vulvar squamous cell carcinoma (VSCC) has two... Show moreVulvar cancer is a relatively rare gynaecologic malignancy with an annual incidence in developed countries of approximately 2 per 100,000 women. Vulvar squamous cell carcinoma (VSCC) has two etiological pathways: a high risk human papillomavirus (HPV)-dependent route, which has usual vulvar intraepithelial neoplasia (uVIN) as a precursor lesion, and an HPV-independent route, which is associated with differentiated VIN (dVIN), lichen sclerosus, and genetic alterations, such as TP53 mutations. Although most cases of early stage vulvar cancer have a good prognosis, recurrence and rapid tumour progression can oc¬cur. The etiology of HPV positive vulvar cancer is quite well understood, but the HPV in-dependent axis remains to be unravelled. This thesis aims to gain knowledge on the origin of this type of vulvar cancer through the study of two mechanisms: genetic and morphological alterations in vulvar cancer. An overview of the literature on genetic and epigenetic changes in vulvar cancer was made. We designed a mass spectrometry based mutation panel and investigated the prevalence of somatic mutations in a cohort of vulvar cancer patients. Also, markers of Epithelial-to-Mesenchimal-Transition such as spindle cell morphology and L1CAM-expression were studied in a large group of patients. These results were related to a worse survival. https://www.gildeprint.nl/flippingbook/4336-vulvar-squamous-cell-carcinoma/Show less
The studies described in this thesis focused on identifying diagnostic and prognostic markers in tumor stage mycosis fungoides (stage IIB) and Sézary syndrome. Sézary syndrome is a type of... Show moreThe studies described in this thesis focused on identifying diagnostic and prognostic markers in tumor stage mycosis fungoides (stage IIB) and Sézary syndrome. Sézary syndrome is a type of cutaneous T-cell lymphoma, characterized by an erythroderma, lymphadenopathy and malignant T cells in skin, lymph nodes and blood. Especially in the early stages of disease, it can be difficult to differentiate Sézary syndrome from erythrodermic inflammatory dermatoses. The studies identified immunohistochemical (TOX), immunophenotypic (CD7, CD26), molecular (STAT4, TWIST1, DNM3/ PLS3) and epigenetic (CMTM2) markers that are useful as additional diagnostic markers to discriminate Sézary syndrome from erythrodermic inflammatory dermatoses. Of the molecular markers, PLS3 expression was an important prognostic factor in Sézary syndrome. In addition, it was shown that the number of tumors and time interval between tumor formation differs greatly among patients with mycosis fungoides stage IIB and these differences correlate with survival. Patients that developed four or more tumors during the first 6 months after diagnosis of stage IIB have a poor prognosis. Show less
The main objective of this thesis was to evaluate the role of new advanced multimodal CT imaging techniques in acute ischemic stroke.Important findings are that collateral assessment with dynamic... Show moreThe main objective of this thesis was to evaluate the role of new advanced multimodal CT imaging techniques in acute ischemic stroke.Important findings are that collateral assessment with dynamic CT angiography (CTA) better predicts radiological outcome and clinical outcome compared with conventional single-phase CTA. Dynamic CTA also enabled us to study dynamic cortical venous outflow in stroke which had not been described before. We have shown that venous outflow, as assessed with dynamic CTA, is a new predictor of functional outcome in acute large vesselvanterior circulation stroke. By combining the extent and velocity of optimal CVF, we observed a decreased risk of poor outcome in patients with good and fast optimal CVF. Moreover, we have demonstrated an interaction between IAT treatment effect and cortical venous filling which could potentially be useful for future treatment decision-making. Show less
Barendregt, J.; Jong, M. de; Haans, J.J.; Hoek, B. van; Hardwick, J.; Veenendaal, R.; ... ; Maljaars, J. 2017
While histopathologic assessment of lymph nodes is a core element of colorectal cancer staging algorithms, the prognostic value of lymph node metastases is restricted. This highlights the need... Show moreWhile histopathologic assessment of lymph nodes is a core element of colorectal cancer staging algorithms, the prognostic value of lymph node metastases is restricted. This highlights the need for approaches that detect occult tumor cells and define their prognostic value, to identify colorectal cancer patients who derive the greatest benefit from therapy. In an attempt to gain insights into prognosis in CRC, this thesis focuses on factors that play a role in the detection or behaviour of occult tumor cells. Especially clinical, pathological and molecular factors of CRC will here be discussed. Show less
Information on prognosis is essential for any physician for providing information to the patient and forms the basis for the decision-making process for therapy. Due to the heterogeneity of the... Show moreInformation on prognosis is essential for any physician for providing information to the patient and forms the basis for the decision-making process for therapy. Due to the heterogeneity of the disease, exploration of prognostic biomarkers in cirrhosis is a challenging, but important aspect of research in the field of chronic liver disease. Besides identifying patients who are at the highest risk of mortality, identification of reliable prognostic biomarkers may also help to improve treatment strategies. The aim of this thesis is to explore novel prognostic biomarkers throughout different stages of chronic liver disease and in acute-on-chronic liver failure (ACLF). Show less
Lay summary: Copeptin is a fragment of the vasopressin precursor, a hormone that is known to be increased in patients with cirrhosis and that plays a role in the development of complications of the... Show moreLay summary: Copeptin is a fragment of the vasopressin precursor, a hormone that is known to be increased in patients with cirrhosis and that plays a role in the development of complications of the disease. Vasopressin is difficult to measure, but copeptin is a more stable molecule and is easier to measure in blood. Sola and Kerbert and colleagues have shown in a series of 361 patients that copeptin is markedly increased in patients with cirrhosis who develop complications during the following 3 months, compared to those patients who do not develop complications. Moreover, copeptin correlates with prognosis. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Show less
