Adverse outcome from LC is particularly associated with male gender, but also the patient's co-morbidity, complexity and urgency of surgery. Risk-adjusted outcome analysis is desirable to ensure an informed consent process.

Objective: This study investigated the effects of oral supplementation of resistant starch (RS) on tumour cell and colonic mucosal cell kinetics and on gene expression in patients with colorectal cancer (CRC), and its potential role in colon cancer prevention. Methods: 65 patients with CRC were randomised to treatment with RS or ordinary starch (OS) and were given starch treatment for up to 4 weeks. Pretreatment and post-treatment biopsies were obtained from the tumour and colonic mucosa, and the effects of the starch treatment on cell proliferation and expression of the cell cycle regulatory genes CDK4 (cyclin-dependent kinase 4) and GADD45A (growth arrest and DNA damage-inducible, alpha) were investigated. Results: The proportion of mitotic cells in the top half of the colonic crypt was significantly lower following RS treatment (3.1 (1.5), mean (SEM)) as compared with OS treatment (13.7 (3.2)) (p = 0.028). However, there was no effect of RS treatment on crypt dimensions and tumour cell proliferation index. There was significant upregulation in expression of CDK4 (p,0.01) and downregulation in expression of GADD45A (p,0.001) in the tumour tissue when compared with macroscopically normal mucosa. Following RS treatment, CDK4 expression in tumours (0.88 (0.15)) was twofold higher than that in the OS group (0.37 (0.16)) (p = 0.02). The expression of GADD45A, which was downregulated in the presence of cancer, was significantly upregulated (p = 0.048) following RS treatment (1.41 (0.26)) as compared with OS treatment (0.56 (0.3)). However, there were no significant differences in the expression of these genes in the normal mucosa following starch treatment. Conclusions: Cell proliferation in the upper part of colonic crypts is a premalignant marker and its reduction by RS supplementation is consistent with an antineoplastic action of this food component. Differential expression of the key cell cycle regulatory genes may contribute to the molecular mechanisms underlying these antineoplastic effects of RS. Trial registration number: ISRCTN93586244.Resistant starch (RS) is defined as the fraction of dietary starch which resists digestion in the small intestine of healthy individuals.1 This undigested starch forms a major substrate for microbial fermentation in the large bowel, leading to the production of short chain fatty acids (SCFAs) including acetate, propionate and butyrate.2 3 RS has a number of physiological effects in the colon, most of which are thought to be due to the SCFAs, particularly butyrate. There is compelling evidence that butyrate causes a dose-dependent suppression of proliferation of colon cancer cell lines, 4-8 and RS has antineoplastic effects against colon cancer in animal models. 9-11Recent studies in rat have shown that feeding RS reduced the incidence and multiplicity of azomethane-induced colon cancers and reduced the tumour-enhancing effects of indigestible protein and red meat.12-14 These protective effects of RS were thought to be secondary to fermentation of RS to butyrate in th...

Self-expanding metal stents are safe and effective in the management of malignant large-bowel obstruction proximal to the splenic flexure. The technical and clinical success rates are comparable with those reported for stenting distal colonic lesions.

The aim of this study was to investigate the differential antineoplastic effects of butyrate in cells with and without a functional mismatch repair and to determine the molecular mechanisms underlying these effects. SW48 colon cancer cells in which the MLH1 gene is silenced by promoter hypermethylation and demethylated SW48 cells in which the MLH1 gene is reexpressed were treated with butyrate (0-5mM) for 8 days and the effects on cell number, MLH1 gene promoter methylation, and expression of two cell cycle regulatory genes, CDK4 and GADD45A, were assessed. Butyrate suppressed viable cell number (P < 0.001) and reduced MLH1 promoter methylation (P < 0.05) in SW48 cells. However, in demethylated SW48 cells, butyrate caused an increase in viable cells (P < 0.05) and promoter methylation (P < 0.05). CDK4 expression was downregulated by butyrate exposure, but the effect was significantly greater for demethylated SW48 cells (P = 0.025). Butyrate treatment caused upregulation of GADD45A expression in SW48 cells but downregulation of GADD45A expression in demethylated SW48 cells (P = 0.045). This study supports the hypothesis that butyrate has more potent antineoplastic effects on colon cancer cells with MLH1 dysfunction. Differential expression of key cell cycle regulatory genes may explain some of the molecular mechanisms underlying these effects.