In the last two decades, treatment of rectal cancer has considerably improved in Europe. Although this applies to most solid malignancies, improvements in the diagnosis and treatment of rectal... Show moreIn the last two decades, treatment of rectal cancer has considerably improved in Europe. Although this applies to most solid malignancies, improvements in the diagnosis and treatment of rectal cancer surpass virtually all others. In the early 1990s, outcome after rectal cancer treatment was poor, with survival and recurrence rates of approximately 45%.1 Nowadays, survival after rectal cancer is sometimes even better than after colon cancer.2 While radiotherapy and chemoradiotherapy play an important role in the current, multidisciplinary treatment of rectal cancer, surgery remains the inevitable cornerstone for cure. For each and every improvement in surgical techniques, (neo)adjuvant treatment schedules, imaging and pathology, clinical trials and population-based audit registrations have played a crucial role. The aim of this thesis is to contribute to further improvements in rectal cancer treatment by investigating the multidisciplinary treatment forms, quality control and European collaboration. Show less
Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal... Show moreTotal mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. Therefore the aim of this thesis was to identify molecular differences between rectal tumors of different stages, using gene expression profiling and genomic analysis. First protocols and data analysis algorithms for a new type of SNP array were developed. These studies showed that reliable LOH and copy number changes could be obtained from both frozen and paraffin embedded material. Consequently SNP arrays were used to type groups of TEM and TME treated samples. Five genomic events were found which could make a clear discrimination between adenomas and carcinomas. Early carcinomas treated by TEM, which were not recognized preoperatively as carcinomas, showed already carcinoma-associated aberrations. Analysis of tree core biopsies per patient showed a large degree of intra- tumor heterogeneity; although a good correlation was obtained between the biopsy with the largest number of aberrations and its corresponding tumor fraction. Gene expression array analysis was performed on the same samples as the SNP array series. A high concordance between chromosomal aberrations and changes in gene expression was observed. Finally a clinical application of these data is discussed in the preoperative staging of rectal tumours. Show less
