This thesis comprises immunophenotypic and molecular studies in several types of cutaneous lymphomas. These studies provide a better definition of the clinicopathologic entities and provide... Show moreThis thesis comprises immunophenotypic and molecular studies in several types of cutaneous lymphomas. These studies provide a better definition of the clinicopathologic entities and provide adjunctive diagnostic markers that may aid in diagnosis of these patients in routine diagnostics, including TOX expression in cutaneous T-cell lymphomas and MYC expression and MYC rearrangements in cutaneous B-cell lymphomas (CBCLs). Also, the results demonstrate that adverse prognostic factors in systemic lymphomas are not directly transferrable to cutaneous lymphoma patients, including TP63 rearrangements in primary cutaneous CD30+ lymphoproliferative disorders and double hit status in CBCL, underlining the importance of a separate classification system for cutaneous lymphomas. Finally, these studies may have consequences for the management and treatment of patients with cutaneous lymphomas, because of the identification of recurrent molecular alterations that could provide attractive targets for novel therapeutics, including MYD88 and CD79B mutations in patients with intravascular large B-cell lymphomas. 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
This thesis consists of a number of studies revolving around the leading research theme, i.e., the derivation of new vectorcardiographic diagnostic & prognostic information from the 12-lead... Show moreThis thesis consists of a number of studies revolving around the leading research theme, i.e., the derivation of new vectorcardiographic diagnostic & prognostic information from the 12-lead electrocardiogram (ECG). Various research questions have been addressed, but most studies use a similar data processing approach, consisting of initial mathematical synthesis of a vectorcardiogram (VCG) from a standard 12-lead ECG, followed by the measurement of general VCG characteristics like maximal QRS- and T vectors, QRS- and T integrals, the spatial QRS-T angle (SA) and the ventricular gradient (VG). Studies focus on methodological as well as on clinical issues, and are discussed in the thesis. Show less
This thesis describes the sentinel node procedure in colorectal carcinoma and the possible value of in-depth analysis of this sentinel node. The sentinel node procedure can be successfully... Show moreThis thesis describes the sentinel node procedure in colorectal carcinoma and the possible value of in-depth analysis of this sentinel node. The sentinel node procedure can be successfully performed in colon carcinoma. However, it is not reliable in rectal carcinoma treated with total mesorectal excision after preoperative short-course radiotherapy, which is the current protocol in The Netherlands and other countries. RT-PCR with CEA, on mRNA extracted from paraffin-embedded sentinel nodes, upstages 17 __ 25 % of patients and accurately predicts lymph node status. A 5-year follow-up of the sentinel node procedure in colon carcinoma -with, but even without, in-depth pathological examination- shows excellent results of the patients in de node-negative group with 100 % cancer-specific 5-year survival and 96 % disease-free 5-year survival. These node-negative patients do not need further treatment. The sentinel node procedure can be easily introduced in clinical practice in every clinic, and should be considered for all patients with colon carcinoma. Show less
Uveal melanoma is a highly malignant intraocular tumor with quite homogeneous tumor tissue and a diffuse leukocytic infiltration. In contrast with many other malignancies, the presence of... Show moreUveal melanoma is a highly malignant intraocular tumor with quite homogeneous tumor tissue and a diffuse leukocytic infiltration. In contrast with many other malignancies, the presence of infiltrating macrophages and T cells is associated with a poor prognosis rather than a good one. The clear link between inflammation and this malignancy provides a paradigm for macrophage plasticity and function. Macrophages in uveal melanoma have an M2-like phenotype and are associated with the loss of one specific chromosome - monosomy 3. The central players involved in this process and discussed include macrophages, T lymphocytes, chemokines and cytokines, including the macrophage-attraction molecules. When a tumor acquires the ability to release significant amounts of macrophage-attraction molecules it causes the expansion of a population of myeloid immature cells that may not only help the tumor to suppress immune reactions but also aid in the construction of new blood vessels for tumor growth. A better understanding of the molecular basis of a local myelomonocytic cell population will bring a better understanding of the immunopathology of this disease and will lead to therapeutic interventions in uveal melanoma. This thesis focuses on the roles of the local inflammatory microenvironment in the development and progression of uveal melanoma. Show less
