Colorectal polyp

Poole EM, Bigler J, Whitton J, Sibert JG, Potter JD, Ulrich CM. (2006) Prostacyclin synthase and arachidonate 5-hpoxygenase polymorphisms and risk of colorectal polyps. Cancer Epidemiol Biomarkers Prev. 15, 502-508. 

Famiiiai adenomatous poiyposis (PAP) (celecoxib) To reduce the number of adenomatous colorectal polyps in FAR as an adjunct to usual care (eg, endoscopic surveillance, surgery). 

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

Celecoxib leads to a significant reduction in the number of colorectal polyps in patients with familial adenomatous polyposis in a 6-months study (Steinbach etal., 2000). 

Somatic mutations of the APC gene are found in more than 70% of all adenomatous polyps and carcinomas of the colon and rectum. It has been estimated that about 50% of the population in the Western world will develop colorectal polyps during a normal life span, as a consequence of/IPC mutations. (See ref 2-6). 

The next great breakthough in new drugs will be those that can prevent or reduce the probability of the first occurrence/ or of a relapse/ of a serious and life-threatening disease. A recent example is the supplemental approval in December 1999 by the EDA for the use of the COX-2 inhibitor celecoxib to reduce the number of adenomatous colorectal polyps in... 

In a placebo-controUed study in 123 patients with colorectal polyps and normal hearing at frequencies of 250-2000 Hz, efiornithine 0.075-0.4 g/m /day for 12 months had no effect on auditory pure-tone thresholds or distortion product otoacoustic emission (14). There was no hearing loss, in contrast to studies with higher dosages. 

Phenolphthalein was once widely used as a laxative for self-treatment, often camouflaged in chocolate and thus hable to abuse or accidental use it is now obsolete. Skin rashes of various types are repeatedly reported, sometimes with pruritus. Pigmentation defects have been described. The most serious albeit rare adverse effect on the skin to have been rehably documented is toxic epidermal necrolysis. A fixed drug eruption with bullous eiythema multiforme is associated with auto-sensitiza-tion, and direct intracellular immunofluorescence is found (19). A hjrpothesis that phenolphthalein might increase the risk of development of adenomatous colorectal polyps has not been confirmed (20). 

Longnecker MP, Sandler DP, Haile RW, Sandler RS. Phenolphthalein-containing laxative use in relation to adenomatous colorectal polyps in three studies. Environ Health Perspect 1997 105(ll) 1210-2. 

There has been concern about the potential for proton pump inhibitors to cause enterochromaffin-hke cell hyperplasia, gastric carcinoid tumors and gastric cancers, colorectal polyps and adenocarcinoma, atrophic gastritis, and intestinal metaplasia in patients with H. pylori infection, and bacterial overgrowth. 

Nagase H, Miyoshi Y, Horii A, Aoki T, Agawa M, Utsunomiya J, et al. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Res 1992 52 4055-7. 

TABLE 1 27-5. American Cancer Society Guidelines for Screening and Surveillance for Early Detection of Colorectal Polyps and Cancer... 

Personal medical history and family history of colorectal polyps, cancer, or other malignancies... 

Celecoxib is a selective COX-2 inhibitor/GI agent that reduces inflammation (e.g., pain, redness, swelling, heat), fever, and pain by inhibiting chemicals in the body that cause inflammation, fever, and pain. This is probably caused by the inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2) isoenzyme. Celecoxib is indicated in relief of symptoms of osteoarthritis relief of symptoms of rheumatoid arthritis in adults management of acute pain in adults treatment of primary dysmenorrhea and reduction of the number of adenomatous colorectal polyps in familial adenomatous polyposis (FAP), as an adjunct to usual care (e.g., endoscopic surveillance, surgery). 

Celecoxib is currently indicated for the relief of signs and symptoms of osteoarthritis and rheumatoid arthritis and to reduce the number of adenomatous colorectal polyps in familial adenomatous polyposis as an adjunct to usual care. Celecoxib is at least as effective as naproxen in the symptomatic management of osteoarthritis and at least as effective as naproxen and diclofenac in the symptomatic treatment of rheumatoid arthritis, and it is less likely to cause adverse Gl effects. Celecoxib appears to be effective in the management of pain associated with both of these arthritic conditions, but effectiveness in acute or chronic pain has not been fully demonstrated. Unlike aspirin, celecoxib does not exhibit antiplatelet activity. Concomitant administration of aspirin and celecoxib may increase the incidence of Gl side effects. Another notable potential drug interaction with celecoxib is its ability, like other NSAIDs, to reduce the blood pressure response to angiotensin-converting enzyme inhibitors. A more detailed discussion of the chemical, pharmacological, pharmacokinetic, and clinical aspects of celecoxib is available (81). 

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. 

Steinbach et al. studied the effect of celecoxib on colorectal polyps in FAP-affected patients during a double-blind, placebo-control study. Seventy-seven patients were treated with celecoxib (100 or 400mg twice daily) or a placebo for 6 months. Endoscopy was performed at the beginning and end of the study, and number and size of polyps were evaluated from photographs and videotapes. Response to therapy was expressed as the mean percent change from baseline. Findings disclosed that after 6 months, those patients who received 400 mg of celecoxib twice a day... 

A randomized trial of vitamins C and E in the prevention of recurrence of colorectal polyps. Cancer Res., 48, 4701, 1988. 

In 2001, Merck started a new study called APPROVe (Adenomatous Polyp PRevention On Vioxx) in order to expand its market by showing the efficacy of Vioxx on colorectal polyps. APPROVe was halted early when the preUminary data showed an increased relative risk of heart attacks and strokes after eighteen months of Vioxx use. The long-term use of Rofecoxib resulted in nearly twice the risk of suffering a heart attack or stroke compared to patients receiving a placebo. 

However bowel preparation should be tailored to the indication, with full or reduced cathartic preparation associated to tagging of fluids or stool. Adequate colonic distension (pneumocolon) is cru-dal for identification of colorectal polyps and differentiation between obstructive cancers and a collapsed segment. Distension is achieved by rectal air or carbon-dioxide insufflation, and standard scout view in lateral and anterior-posterior projections are acquired to verify the distension of the entire colon. The intravenous administration of a muscle rdaxant, to reduce large bowel movement and... 

Pass R, Do S, Hixson LI (1993) Fatal hyperphosphatemia following Fleet Phospo-Soda in a patient with colonic ileus. Am 1 Gastroenterol 88 929-932 Fenlon HM, Nunes DP, Schroy PC S " et al (1999) A comparison of virtual and conventional colonoscopy for the detection of colorectal polyps. N Engl J Med 341 1496-1503... 

Johnson CD, Harmsen WS, Wilson LA et al (2003) Prospective blinded evaluation of computed tomographic colonography for screen detection of colorectal polyps. Gastroenterology 125 311-319... 

Macari M, Milano A, Lavelle M et al (2000) Comparison of time-efficient CT colonography with two- and three-dimensional colonic evaluation for detecting colorectal polyps. AJR Am J Roentgenol 174 1543-1549... 

Pickhardt PJ, Taylor AJ (2006) Extracolonic findings identified in asymptomatic adults at screening CT colonography. AJR Am J Roentgenol 186 718-728 Pineau BC, Paskett ED, Chen GJ et al (2003) Virtual colonoscopy using oral contrast compared with colonoscopy for the detection of patients with colorectal polyps. Gastroenterology 125 304-310... 

In a primary two-dimensional (2D) approach, axial helical CT images are used for the detection of colorectal polyps or colorectal cancer. If these images are not conclusive at a certain location, either multi-planar reformatted (MPR) images (coronal, sagittal or oblique) or 3D rendered images can be used for problem solving (i.e. differentiating between abnormalities and normal anatomy). 

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