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
In contrast with the intuitive feeling of physicians many worrisome MRI findings do not correlate with patient outcome in patients with sciatica. Physicians should for example not automatically... Show moreIn contrast with the intuitive feeling of physicians many worrisome MRI findings do not correlate with patient outcome in patients with sciatica. Physicians should for example not automatically ascribe persistent or recurrent symptoms of sciatica to the presence of abnormalities visible on MRI. This thesis enables physicians to reshape the mindset of many persons thinking that knowing imaging findings can only be good. Seeing MRI abnormalities of patients with sciatica should not always be believing. 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
It can be concluded from this thesis that high-grade osteosarcoma is at clinical, pathological and molecular level a heterogeneous disease. To treat high-grade osteosarcoma, neo-adjuvant... Show moreIt can be concluded from this thesis that high-grade osteosarcoma is at clinical, pathological and molecular level a heterogeneous disease. To treat high-grade osteosarcoma, neo-adjuvant chemotherapy should be combined with radical surgery, irrespective the localization. There are only 4 effective cytostatic agents for osteosarcoma treatment: methotrexate, doxorubicin, cis-platin and ifosfamide. Patients with pulmonary metastases should receive surgery in case of resectable disease, whereas the use of chemotherapy is not of proven value. Patients with irresectable metastatic osteosarcoma should be offered phase-I studies, because no response can be expected from other conventional cytostatic drugs. New drugs, such as the monoclonal antibody trastuzumab against HER2 is not supported by us, because we did not find this receptor on osteosarcoma cells. At molecular level, a disturbed Wnt signalling, an abnormal cell c ycle regulation and a disturbed p53/apoptotic pathway was present in osteosarcoma cells. The hypothesis is that failure of the mesenchymal stem cell to differentiate into the osteoblastic lineage, due to abnormal proliferation and lack of differentiation commitment results in chromosomal instability, which is the hallmark of osteosarcoma. In Patients with an inactive Wnt3a/_-catenin signalling the proteasome inhibitor bortezomib might be a candidate drug, to explore its suggested differentiation inducing properties. Show less
