http://repub.eur.nl/res/aut/11043/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/21426/ 2010-11-09T00:00:00Z Background:The optimal treatment of desmoid tumours is controversial. We evaluated desmoid management in Dutch familial adenomatous polyposis (FAP) patients. Methods:Seventy-eight FAP patients with desmoids were identified from the Dutch Polyposis Registry. Data on desmoid morphology, management, and outcome were analysed retrospectively. Progression-free survival (PFS) rates and final outcome were compared for surgical vs non-surgical treatment, for intra-abdominal and extra-abdominal desmoids separately. Also, pharmacological treatment was evaluated for all desmoids. Results:Median follow-up was 8 years. For intra-abdominal desmoids (n=62), PFS rates at 10 years of follow-up were comparable after surgical and non-surgical treatment (33% and 49%, respectively, P=0.163). None of these desmoids could be removed entirely. Eventually, one fifth died from desmoid disease. Most extra-abdominal and abdominal wall desmoids were treated surgically with a PFS rate of 63% and no deaths from desmoid disease. Comparison between NSAID and anti-estrogen treatment showed comparable outcomes. Four of the 10 patients who received chemotherapy had stabilisation of tumour growth, all after doxorubicin combination therapy. Conclusion:For intra-abdominal desmoids, a conservative approach and surgery showed comparable outcomes. For extra-abdominal and abdominal wall desmoids, surgery seemed appropriate. Different pharmacological therapies showed comparable outcomes. If chemotherapy was given for progressively growing intra-abdominal desmoids, most favourable outcomes occurred after combinations including doxorubicin.British Journal of Cancer advance online publication, 9 November 2010; doi:10.1038/sj.bjc.6605997 www.bjcancer.com. http://repub.eur.nl/res/pub/8371/ 2005-01-01T00:00:00Z BACKGROUND: Chronic ulcerative colitis (CUC) is associated with increased risk of developing colon cancer through a dysplasia (intraepithelial neoplasia)-carcinoma sequence. AIMS: To investigate the expression of apoptosis and inflammatory related proteins in CUC. METHODS: The expression of proteins involved in apoptosis and inflammation (inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), Bcl-xl, Fas, and active caspase 3) was investigated and compared with that seen in sporadic colon carcinoma. RESULTS: COX-2 was negative in the epithelium of all samples. iNOS was clearly present in inflammatory areas in CUC epithelium, weakly expressed in dysplasia, and absent or weakly expressed in tumour cells. Bcl-xl was absent in CUC, increased in dysplasia, and highly expressed in most carcinomas. Fas expression was positive in the surface epithelium of CUC, dysplasia, and most tumour cells. Activated caspase 3 was weakly positive in all samples, indicating limited apoptosis. Compared with CUC associated carcinoma, iNOS was consistently expressed in sporadic colon carcinoma cells, whereas Bcl-xl was almost absent in these tumour cells and Fas was only weakly expressed. Activated caspase 3 was present in normal mucosal samples and some tumour cells. CONCLUSION: Apoptosis related proteins--particularly iNOS, Bcl-xl, and Fas-show a distinct pattern of expression in the CUC to carcinoma sequence, which differs from that seen in sporadic carcinoma, but bears a striking resemblance to that seen during neoplastic progression in Barrett's oesophagus. These results support a causal role for chronic inflammation in cancer development in CUC, and treatment of ulcerative colitis should aim to minimise inflammation.