STUDIES ON THE MORPHOGENESIS OF ADENOMATOUS POLYPS IN THE HUMAN COLON.
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Explore the source record for details and available documents.
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Colorectal cancer is the second-most frequent cause of cancer mortality in the United States. Human epidemiology and laboratory studies indicate that aspirin may be an effective colorectal cancer chemopreventive agent. This study was designed to determine whether treatment with 81 mg of aspirin per day for 3 months would alter two putative surrogate end point biomarkers of chemoprevention of colorectal cancer [i.e., mucosal prostaglandin E2 (PGE2) formation and transforming growth factor alpha (TGF-alpha) expression] in normal-appearing rectal mucosa from individuals with a history of adenomatous polyps. Rectal biopsies were obtained by flexible sigmoidoscopy at three sequential time points: (a) after a 1-month placebo run-in period (baseline), (b) after 3 months of ingesting 81 mg of aspirin (as a single tablet) once per day, and (c) after 3 months of ingesting a placebo tablet once per day (washout period). Daily aspirin significantly suppressed PGE2 formation, but this significant suppression was completely reversed when aspirin was withdrawn. The extent of TGF-alpha staining in rectal crypts was also reduced significantly (P = 0.039) by daily aspirin. After a 3-month placebo-washout period, however, the mean extent of TGF-alpha staining was not significantly different from either baseline or the aspirin time point. Thus, 81 mg of aspirin daily significantly reduced rectal mucosal PGE2 formation and TGF-alpha expression in patients with a history of adenomatous polyps. These putative surrogate end point biomarkers may be useful intermediate end points in future colorectal cancer chemoprevention trials.
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The reproducibility of polyp localization and size measurements was tested to evaluate the reliability of observations during follow-up examinations of sigmoidoscopically diagnosed polyps. Our findings suggest that 25% of polyps less than 5 mm in diameter but only 5% of those larger than 5 mm are likely to be missed by a single endoscopic examination. Localization measurements made during insertion and withdrawal of the endoscope on different days of examination diverged proximal to 30 cm from the anal ring during repeat colonoscopy. Otherwise, reproducibility was good, demonstrating that sigmoidoscopy may be a fairly accurate procedure for evaluation of site and size of polyps during follow-up studies.
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To determine the frequency and clinical significance of oncogene abnormalities in colon cancer, deoxyribonucleic acids from 45 colon carcinomas and 15 benign adenomas were hybridized with 14 different protooncogene probes. Abnormalities of oncogenes were found in 22% of cancers at the time of resection. Amplification of c-myc or c-erbB-2 and allelic deletion of c-ras-Ha or c-myb were the most frequent abnormalities. The presence of altered oncogenes did not correlate with Dukes' stage, tumor progression, or patient survival after resection. One adenoma had an allelic deletion of the c-myb oncogene which was not seen in either the normal colon or an adjacent carcinoma. These data indicate that the spectrum of altered protooncogenes in colon carcinoma is similar to that of other adenocarcinomas, and that unstable oncogenes can be found before overt malignancy develops.
To detect an early colon carcinoma in its stage of carcinoma in situ, colonoscopic examinations with removal of all adenomas of the left colon (particularly of the sigmoid tract and rectum), followed by histological and biochemical evaluations, have been performed on 30 patients. Two-thirds of the adenomas examined presented histological patterns of tubular, tubulovillous, and villous adenomas; those with moderate or severe dysplasia were at high risk of neoplastic transformation. Measurement of estradiol (ER) and progesterone (PR) receptors was performed in the cytosol and in the nuclei of solitary and multiple adenomas and in those with synchronous carcinomas using the dextran-coated-charcoal (DCC) method. Steroid receptors were usually found in the cytosol of the large polyps of male rather than female patients (46% vs 11%) and in the cytosol of the adenomas with moderate or severe dysplasia in male patients. Malignant lesions usually possessed both ER and PR in the cytosol and nuclear fraction. These findings led to hypothesize that patients with adenomas of the colorectal tract with moderate or severe dysplasia and nuclear steroid receptors should be considered at high risk for colon carcinoma and therefore need a special follow-up program.
General practitioners may gain valuable information from the use of open access endoscopy. The benefit to the individual patient depends on the interpretation of the endoscopy findings and the subsequent action. The aim of the study was to determine GPs response to open access endoscopy findings of three conditions with possible malignant complications: Barrett's oesophagus, gastric ulcer and colonic adenomatous polyps. The study took place at Ninewells Hospital, Dundee. Using the endoscopy unit's records for the year, 1 January 1995 to 31 December 1995, all patients having had an open access upper gastro-intestinal endoscopy or sigmoidoscopy were identified. Case-notes were reviewed of patients who had Barrett's oesophagus, gastric ulcer or colonic polyps diagnosed. During the year, 1158 upper gastro-intestinal endoscopies and 293 sigmoidoscopies were performed by the open access service. The referral rates for the conditions were as follows: Barrett's oesophagus 56%; Gastric ulcers 56%; Adenomatous polyps 88%; Non adenomatous polyps 12.5%. The provision of guidelines does not ensure a high referral rate, education is a vital partner.
To evaluate the neoplastic risk of polyps of the right hemicolon we assigned 202 polyps larger than 4 mm, consecutively resected, to two groups according to their location, proximal or distal to the splenic flexure. We compared sex and age of the patients and the following characteristics of the polyps: size 10 mm and over, adenomatous and villous component, presence of severe dysplasia and absence of a stalk. We found that polyps in the proximal colon were less frequently dysplastic and smaller; on the other side fewer of them had a stalk. A significant rightward shift was observed in the male patients over 65 years old. Apparently right hemicolon polyps are less prone to overt clinical bleeding.
The purpose of this study was to determine the rate of cancer in a modern series of colorectal polyps. All pathology reports from colon and rectal polyps from 1999 to 2002 were reviewed. Reports of bowel resections, cancer-free polyps, and polyp-free mucosal biopsies were excluded. Polyps were grouped by size, and the rate of adenocarcinoma was determined. x2 was used for analysis. A total of 4,443 polyps were found, of which 3,225 were adenomatous [2,883 (89.4%) tubular adenomas, 399 (9.3%) tubulo-villous adenomas, 32 (1.0%) villous adenomas, and 11 (0.3%) carcinomas]. The rate of adenocarcinoma by size was 0.07 per cent for polyps <1 cm, 2.41 per cent for polyps 1-2 cm, and 19.35 per cent for polyps >2 cm, representing significantly fewer cancers for each category of polyp size than the accepted standard. The rate of carcinoma in colon polyps is much lower than previously thought and currently stated in many texts. These data do not alter the recommendations for polyp removal, however, failure to retrieve a specimen in a polyp <1 cm in size is unlikely to have an adverse outcome because the chances of malignancy are very low.
This study was initiated to evaluate the efficacy of negative contrast-enhanced microcomputed tomography (microCT) colonography for the noninvasive detection of colonic tumors in living mice. After colonic preparation, 20 anesthetized congenic mice were scanned with high-resolution microCT. Images were displayed by using commercial visualization software and interpreted by two gastrointestinal radiologists, who were unaware of tumor prevalence and findings at gross pathology. Two-dimensional multiplanar images were assessed by using a five-point scale to distinguish colonic tumors (polyps) from fecal pellets (5 = definitely a tumor, 4 = probably a tumor, 3 = indeterminate, 2 = probably not a tumor, 1 = definitely not a tumor). Gross pathologic evaluation of excised mouse colons served as the reference standard. Data analysis included dichotomizing results, with 1-2 indicating no tumor and 3-5 indicating tumor and also receiver operator characteristic curve analysis with area under the curve for threshold-independent assessment. A total of 41 colonic polyps in 18 of the 20 mice were identified at gross examination on necropsy, of which 30 measured 2-5 mm and 11 measured <2 mm in size. The pooled per-polyp sensitivity for lesions >2 mm was 93.3% (56/60). The pooled per-mouse sensitivity for polyps >2 mm was 97.1% (33/34). Pooled specificity for distinguishing fecal pellets from tumor was 98.5% (65/66). The combined area under the curve from receiver operator characteristic curve analysis was 0.810 +/- 0.038 (95% confidence interval, 0.730-0.890). These findings indicate that accurate noninvasive longitudinal monitoring of colon tumor progression or response to various therapies is now technically feasible in live mice by using this microCT colonography method.