Colon polyps

Fiber components are the principal energy source for colonic bacteria with a further contribution from digestive tract mucosal polysaccharides. Rate of fermentation varies with the chemical nature of the fiber components. Short-chain fatty acids generated by bacterial action are partiaUy absorbed through the colon waU and provide a supplementary energy source to the host. Therefore, dietary fiber is partiaUy caloric. The short-chain fatty acids also promote reabsorption of sodium and water from the colon and stimulate colonic blood flow and pancreatic secretions. Butyrate has added health benefits. Butyric acid is the preferred energy source for the colonocytes and has been shown to promote normal colonic epitheUal ceU differentiation. Butyric acid may inhibit colonic polyps and tumors. The relationships of intestinal microflora to health and disease have been reviewed (10). 

Prolonged hypergastrinemia leading to the development of colonic polyps and potentially adenocarcinoma in rats was a concern that has proven to be unfounded with long-term use in humans.19 The FDA has stated that there is insufficient evidence linking PPI use to atrophic gastritis, intestinal metaplasia, or gastric cancer.20... 

Cole AR et al. Proteomic analysis of colonic crypts from normal, multiple intestinal neoplasia and p53-null mice a comparison with colonic polyps. Electrophoresis 2000 21 1772-1781. 

The FDA approved this selective cyclooxigenase (COX)-2 inhibitor (Vioxx) for the treatment of pain and inflammation in 1999. This NSAID demonstrated to have a lower risk of side effects such as gastrointestinal ulcers and bleeding than nonse-lective COX inhibitors, for example, ibuprofen. In 2004, a long-term study of Vioxx in patients at increased risk of colon polyps was halted because of an increased cardiovascular risk (heart attack, stroke) in the rofecoxib group. Subsequently, Merck withdrew the drug from the world market at the end of September 2004 [46]. 

There is a disease termed hereditary polyposis. Victims develop a very large number of polyps in their colons, sometimes several thousand. Since the development of a colon polyp is the first step on the road to colon carcinoma, they are at high risk of colon cancer. The associated mutation is in a gene known as the APC gene. 

Fig. 2.9. A Average Raman spectra of hyperplastic (n = 20 solid line) and adenomatous (n = 34 broken line) colon polyps collected ex vivo (power = 200 mW 30-s collection time). B Average Raman spectra of hyperplastic (n = 9 solid line) and adenomatous (n = 10 broken line) colon polyps collected in vivo (power = 100mW 5-s collection time). The spectra have been intensity corrected, wavelength calibrated, and fluorescence background subtracted (modified from [25], with permission)...

Zonios G, Perelman LT, Backman VM, Manoharan R, Fitzmaurice M, Van Dam J, Feld MS. Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo. Applied Optics 1999, 38, 6628-6637. 

Additionally, patients with familial adenomatous polyposis, an autosomal-dominant disease characterized by numerous small intestinal and colonic polyps with a nearly universal progression to colon cancer, have a favorable response to NSAIDs. Administration of NSAID (usually sulindac) to patients with this disorder reduces the number and size of polyps (DuBois et al., 1996). Recent biochemical evidence indicates that colon polyps and colon cancer are frequendy associated with induction of Cox-2 in the lesion as assessed by expression of Cox-2 mRNA and protein. Such induction appears to correlate with growth of the lesion, and inhibition of Cox-2 correlates with apoptosis of the involved cells (Gupta and DuBois, 1998). 

However, despite the firm experimental basis and encouraging clinical studies, prophylaxis with NSAIDs to prevent colon cancer in patients who have polyps or in the population in general is notjustified because of the GI toxicity of such therapy. With the introduction of Cox-2 inhibitors, it now is feasible to test the hypothesis that inhibition of Cox-2 over prolonged periods of time would be protective against the development of colon polyps. Since it is well accepted that colon polyps are precancerous lesions, the prevention of polyps should translate into a reduction in the incidence of colon cancer. 

Several studies using rofecoxib or celecoxib have been contemplated or begun. Both Cox-2 inhibitors are being studied in patients with familial adenomatous polyposis, and results with celecoxib have recently been reported (Steinbach et al., 2000). Also, there are plans to evaluate the ability of Cox-2 inhibitors to reduce the recurrence of polyps in patients who have had sporadic colonic polyps surgically removed. Ultimately, one would like to determine whether therapy with Cox-2 inhibitors could be used prophylactically in high-risk patients to prevent the development or recurrence of colon cancer. 

Cell proliferation Histology Aberrant crypt foci (colon polyps precursors)... 

Methylthioninium chloride marking of a colonic polyp resulted in an inflammatory mass with small arteries showing both segmental and circumferential fibrinoid necrosis with thrombosis (5). 

Borczuk AC, Petterino B, Alt E. Inflammatory mass with fibrinoid necrosis of vessels caused by methylene blue marking of a colonic polyp. Cardiovasc Pathol 1998 7 267-9. 

Abe K, Hakomori S, Ohshiba S. Differential expression of difucosyl type 2 chain (LeY) defined by monoclonal antibody AH6 in different locations of colonic epithelia, various histological types of colonic polyps, and adenocarcinomas. Cancer Res 1986 46 2639-2644. 

Two recent studies on aspirin and its role in colonic polyps have shown benefit." " Sandler et al." performed a randomized, double-blind trial with the objective of determining the effect of aspirin on the incidence of colorectal adenomas. They randomly assigned 635 patients with a prior histoiy of CRC to receive 325 mg of aspirin daily or placebo. Their results disclosed that... 

Along this same vein, Matsuhashi et al. described a rapidly growing invasive rectal cancer in 1 of 15 patients treated with sulindac for sporadic adenomatous colorectal polyps 16 months after sulindac treatment. They found that the adenomatous polyp had responded only partially to sulindac, and the rectal cancer developed following sulindac therapy and it showed immunostaining for COX-2. They concluded that while short-term sulindac therapy appears to cause some adenomatous colon polyps to regress, nevertheless it may not reliably prevent CRC in certain patients. 

Matsuhashi, N., Nakajima, A., Shinohara, K., Oka, T., and Yazaki, Y., Rectal cancer after sulindac therapy for a sporadic adenomatous colonic polyp,Hot. J. Gastroenterol, 93, 2261-2266, 1998. 

In colonic polyps, the oncogenic pathways are those of the APC deletion and BRAF and CTNNBl (catenin-beta) mutations whereas, the mutator phenotype is induced by numerous single nucleotide substitutions [2099]. 

Gourtsoyiannis et al. 2004). This method can be used to detect colonic polyps and differentiate them from residual stool. Polyps present with variable degrees of enhancement, while residual stool do not exhibit any enhancement at all (Papanikolaou et al. 2003 Lauenstein et al. 2001). 

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