With the introduction of population-based screening, early-stage colorectal cancers (T1CRCs) are increasingly detected. The treatment of patients with T1CRC is complex, as these tumors have... Show moreWith the introduction of population-based screening, early-stage colorectal cancers (T1CRCs) are increasingly detected. The treatment of patients with T1CRC is complex, as these tumors have metastatic potential despite their early stage. As a result, local organ-sparing endoscopic tumor resection is not always sufficient, thereby giving rise to various challenges throughout the entire treatment process.The overarching goal of this thesis is to improve clinical care for T1CRC patients. Part 1 is centered around the biology and translational potential of the tumor microenvironment, and in particular cancer-associated fibroblasts (CAFs), in T1CRC. The studies in this part show that CAFs in T1CRCs exhibit T1 stage-specific phenotypic traits and can promote cancer cell invasion in T1CRC through diverse mechanisms. These findings provide promising leads for developing better predictors of metastasis, which can be used to determine which T1CRC patients will (not) benefit from major bowel surgery.Part 2 focuses on the clinical aspects of T1CRC treatment. The studies in this part show that local endoscopic tumor resection has become a mature alternative to surgery, from both the patient’s and oncological perspective. However, further optimizations of local resection techniques and surveillance thereafter are needed to increase the use of organ-sparing treatment for T1CRC patients. Show less
Kuiper, T.; Oijen, M.G.H. van; Velthuysen, M.F. van; Lelyveld, N. van; Leerdam, M.E. van; Vleggaar, F.D.; Klumpen, H.J. 2020
Purpose Rectal neuroendocrine tumours (NETs) often present as an incidental finding during colonoscopy. Complete endoscopic resection of low-grade NETs up to 10 mm is considered safe. Whether this... Show morePurpose Rectal neuroendocrine tumours (NETs) often present as an incidental finding during colonoscopy. Complete endoscopic resection of low-grade NETs up to 10 mm is considered safe. Whether this is also safe for NETs up to 20 mm is unclear. We performed a nationwide study to determine the risk of lymph node and distant metastases in endoscopically removed NETs. Methods All endoscopically removed rectal NETs between 1990 and 2010 were identified using the national pathology database (PALGA). Each NET was stratified according to size, grade and resection margin. Follow-up was until February 2016. Results Between 1990 and 2010, a total of 310 NETs smaller than 20 mm were endoscopically removed. Mean size of NETs was 7.4 mm (SD 3.5). In 49% of NETs (n = 153), no grade (G) could be assessed from the pathology report, 1% was G2 (n = 3), and the remaining NETs were G1. Median follow up was 11.6 years (range 4.9-26.0). During follow-up, 30 patients underwent surgical resection. Lymph node or distant metastasis was seen in 3 patients (1%) which all had a grade 2 NET. Mean time from endoscopic resection to diagnosis of metastases was 6.1 years (95% CI 2.9-9.2). Conclusion No lymph node or distant metastases were seen in endoscopically removed G1 NETs up to 20 mm during the long follow-up of this nationwide study. This adds evidence to the ENET guideline that endoscopic resection of G1 NETs up to 20 mm appears to be safe. Show less
Langers, A.M.J.; Boonstra, J.J.; Hardwick, J.C.H.; Kraan, J. van der; Sarasqueta, A.F.; Vasen, H.F.A. 2019
